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Abstract ID: 1
First Name: Mehrak
Last Name: Javadi Paydar
Abstract Title: PIOGLITAZONE ANTICONVULSANT EFFECT IS MEDIATED THROUGH INVOLVEMENT OF NITRIC OXIDE IN MICE
  
 Abstract:
 PIOGLITAZONE ANTICONVULSANT EFFECT IS MEDIATED THROUGH INVOLVEMENT OF NITRIC OXIDE IN MICE Mehrak Javadi-Paydar, Mohadeseh Adabi Mohazab, Ahmad Reza Dehpour a) Brain and Spinal Injury Repair Research Center, Tehran University of Medical Sciences; b) Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran In the present study, the effects of acutely administered pioglitazone on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were evaluated in mice. PTZ was administered intravenously. A single dose of pioglitazone (10, 20, 40 and 80 mg/kg, p.o.) was administered 4 hours prior to induction of seizures. For determination of possible role of peroxisome proliferator activated receptor gamma (PPAR-γ) and nitric oxide pathway in this effect, the effects of a PPAR-γ antagonist, GW9662 (2 mg/kg); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.3, 1, 3, and 10 mg/kg); a specific iNOS inhibitor, aminoguanidine (100 mg/kg, i.p.) or a nitric oxide precursor, L-arginine (30, 60, 100 and 200 mg/kg, i.p.) were investigated on the anticonvulsant effect of this pioglitazone. Pioglitazone (40 and 80 mg/kg) increased the threshold of PTZ-induced seizure in a dose-dependent, and time-dependent manner. GW9662 reversed the anticonvulsant effect of pioglitazone (40 mg/kg). L-NAME (1, 3 and 10 mg/kg) and also aminoguanidine (100 mg/kg) inhibited the anticonvulsant effect of pioglitazone (40 mg/kg); whereas L-arginine (100 mg/kg), co-administered with a subeffective dose of pioglitazone (20 mg/kg), potentiated the seizure threshold. In Conclusion, the present study demonstrates the anticonvulsant effect of acute pioglitazone on PTZ-induced seizure in mice. This effect was reversed by PPAR-γ antagonist, and both a specific- and a non-specific nitric oxide synthase inhibitors, and augmented by nitric oxide precursor, L-arginine. These results support that the anticonvulsant effect of pioglitazone is mediated through receptor-mediated mechanism and also, at least partly, through the nitric oxide pathway.
Abstract ID: 3
First Name: Callum
Last Name: Hicks
Abstract Title: IN VIVO CHARACTERISATION OF SOC-1: A NOVEL PROSOCIAL COMPOUND
  
 Abstract:
 IN VIVO CHARACTERISATION OF SOC-1: A NOVEL PROSOCIAL COMPOUND. Hicks, C.1; Bowen, M.T.1; Ramos, L.1; Jorgensen, W.1; Kassiou, M.1; Hunt, G.E.3; McGregor, I.S.1. 1School of Psychology, University of Sydney, Sydney, N.S.W. 2006, Australia; 2Brain and Mind Research Institute, University of Sydney; 3Discipline of Psychiatry, University of Sydney, Concord Hospital, Concord, N.S.W. 2139, Australia. Psychiatric disorders (e.g. autism) may benefit through the development of compounds that act to stimulate social behaviour. Accordingly, our drug discovery program is focused on compounds that modulate brain oxytocin, vasopressin and neurosteroid systems to facilitate social behaviour in rodents. SOC-1 evolved from our program producing non-peptide compounds that interact with brain oxytocin receptors. SOC-1 (5 mg/kg, IP) caused similar brain Fos expression to the non-peptide oxytocin agonist/vasopressin antagonist WAY 267,464 (100 mg/kg, IP) and oxytocin itself (1 mg/kg, IP), with pronounced expression in the supraoptic and paraventricular hypothalamic nuclei, lateral parabrachial nucleus and nucleus of the solitary tract, and greater activation in the lateral septal nucleus and medial preoptic area. In the ’classic’ social interaction test, SOC-1 (5 mg/kg) increased the time rats spent lying adjacent to a novel conspecific. The same dose also increased the time rats spent interacting with a caged live rat, relative to a caged dummy rat, in a social preference paradigm. These prosocial effects appeared to be independent of a general anxiolytic effect as SOC-1 failed to affect behaviour on the elevated plus-maze. Biotelemetry studies in rats showed that SOC-1 (5 mg/kg) had a strong hypothermic effect, similar to oxytocin (1 mg/kg), but unlike oxytocin did not cause reductions in heart rate. SOC-1 also reversed the hyperthermia seen during acute social interaction. Pretreatment with an oxytocin receptor antagonist (Pfizer Compound 25, 10 mg/kg, IP), vasopressin 1a receptor antagonist (SR 49059, 10 mg/kg, IP) or a benzodiazepine antagonist (flumazenil, 10 mg/kg, IP) did not prevent the hypothermic effects of SOC-1. Ongoing receptor binding studies suggest that SOC-1 actually has low affinity for oxytocin and vasopressin receptors and may therefore be acting on an upstream target to indirectly modulate these systems. Overall, SOC-1 is a novel prosocial compound with an oxytocin-like profile of brain activation and body temperature. It represents a novel research tool for examining in vivo the mechanisms and neural circuitry underlying social behaviour.
Abstract ID: 4
First Name: Khemraj
Last Name: Hirani
Abstract Title: CHEMOPROTECTIVE POTENTIAL OF COCCINIA INDICA AGAINST CYCLOPHOSPHAMIDE INDUCED OXIDATIVE STRESS AND GENOTOXICITY IN BONE MARROW
  
 Abstract:
 CHEMOPROTECTIVE POTENTIAL OF COCCINIA INDICA AGAINST CYCLOPHOSPHAMIDE INDUCED OXIDATIVE STRESS AND GENOTOXICITY IN BONE MARROW Hirani K*, Nitharwal R#, Karchuli MS#, Patel H#, Ugale RR# *Sylvester Comprehensive Cancer Center, University of Miami Hospitals and Clinics, Miller School of Medicine, USA. #Division of Neuroscience, Department of Pharmacology, S.K.B.College of Pharmacy, Kamptee, Nagpur 440024, India. Although cyclophosphamide (CP), an alkylating agent is used in the treatment of cancer owing to its broad spectrum efficacy, its metabolites exhibits severe undesired toxicities in normal cells. The present study was aimed to investigate the chemoprotective potential of Coccinia indica against CP induced oxidative stress and genotoxocity in bone marrow. Animals were orally pre-treated with Coccinia indica extract (200, 400 mg/kg) for five consecutive days. On 5th day these animals were injected with CP (50 mg/kg i.p) and sacrificed after 24 hr. for the evaluation of oxidative stress, micronucleus formation and chromosomal aberrations. We found that the CP induced increase in the serum biomarker enzymes like alkaline phosphatase (ALP), alkaline aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced by Coccinia indica extract. We also found that the CP significantly increased malondialdehyde (MDA) and decreased catalase and glutathione (GSH) levels in brain and it was significantly reversed by Coccinia indica extract (400 mg/kg). Further, pre-treatment with Coccinia indica extract (200, 400, 600 mg/kg) significantly and dose dependently reduced micronuclei formation and incidence of aberrant cells. Thus, the present results indicate the chemoprotective potential of Coccinia indica extract against CP induced oxidative stress and genotoxicity in bone marrow.
Abstract ID: 5
First Name: Brennan
Last Name: Eadie
Abstract Title: IMPAIRED CONTEXT DISCRIMINATION AND NMDA RECEPTOR EXPRESSION AND FUNCTION IN THE DENTATE GYRUS OF A MOUSE MODEL OF FRAGILE X SYNDROME.
  
 Abstract:
 IMPAIRED CONTEXT DISCRIMINATION AND NMDA RECEPTOR EXPRESSION AND FUNCTION IN THE DENTATE GYRUS OF A MOUSE MODEL OF FRAGILE X SYNDROME. Eadie, B.1,2; Cushman, J.3; Majaess, N.2; Bostrom, C.2; Kannangara, T.2; Fanselow, M.3; Christie, B.2. 1.MD/PhD Program, University of British Columbia, Vancouver, BC, Canada. 2.Division of Medical Sciences, University of Victoria, Victoria, BC, Canada. 3.Department of Psychology, University of California, Los Angeles, CA, USA. Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. This X-linked disorder is caused by the transcriptional repression of a single gene, Fmr1. The loss of Fmr1 transcription prevents the production of Fragile X mental retardation protein (FMRP), which in turn disrupts the expression of a variety of key synaptic proteins. A clear link between synaptic dysfunction and behavioral impairment has been elusive despite the fact that several animal models of FXS have been generated. Here we report that Fmr1 knockout mice exhibit impaired bidirectional NMDAR (N-methyl-D-aspartate receptor)-dependent synaptic plasticity, NMDAR subunit expression and NMDAR-mediated currents in the dentate gyrus (DG) of the hippocampus. Interestingly, mice lacking the Fmr1 gene show impaired performance in a context discrimination task that normally requires functional NMDARs in the DG. These data indicate that loss of FMRP results in significant NMDAR dysfunction in the DG and associated impairments in behavior.
Abstract ID: 6
First Name: Ine
Last Name: Rayen
Abstract Title: DEVELOPMENTAL FLUOXETINE EXPOSURE, BUT NOT PRENATAL STRESS, DEMASCULINIZES SEXUAL BEHAVIOR IN MALES, BUT HAS NO EFFECT ON SEXUAL BEHAVIOR IN FEMALES.
  
 Abstract:
 DEVELOPMENTAL FLUOXETINE EXPOSURE, BUT NOT PRENATAL STRESS, DEMASCULINIZES SEXUAL BEHAVIOR IN MALES, BUT HAS NO EFFECT ON SEXUAL BEHAVIOR IN FEMALES. Rayen I.; Charlier T.D.; Balthazart J.; Steinbusch H.W.M.; Pawluski J.L. School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands; University of Lige, GIGA-Neurosciences, 1 avenue de l’Hpital (Bat. B36), B-4000 Lige, Belgium; EURON, European Graduate School for Neuroscience.Depression during pregnancy and postpartum is a significant health problem and affects up to 20% of women. While selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression, the combined effect of maternal depression and perinatal SSRI exposure on offspring development is poorly investigated. Here, our aim was to determine the role of exposure to fluoxetine during development on sexual behavior in offspring using a rodent model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were chronically treated throughout lactation with either fluoxetine (5mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Four groups of male and female offspring were obtained: 1) prenatal stress + fluoxetine, 2) prenatal stress + vehicle, 3) fluoxetine alone, and 4) vehicle alone. In Experiment 1, we assessed ano-genital (AG) distance in juvenile male and female offspring. In Experiment 2, adult male and female offspring were tested to assess the effect of developmental fluoxetine exposure and prenatal stress on sexual behavior. Maternal fluoxetine exposure significantly decreased AG distance in juvenile male offspring, regardless of prenatal stress. In adult male offspring, maternal fluoxetine treatment, regardless of exposure to prenatal stress, significantly increased the latency to first intromission, decreased the number of intromissions and tended to increase the latency to the first ejaculation. In adult female offspring, preliminary results show that prenatal stress, regardless of maternal fluoxetine treatment, significantly increased the female lordosis response to a male mount and decreased the number of rejections by the female. These results provide important evidence for the long-term impact of maternal adversity and maternal fluoxetine use on the development of fundamental physiological systems in male and female offspring. Further work will investigate the neurobiological plasticity underlying these behavioral effects.
Abstract ID: 7
First Name: Oded
Last Name: Meiron
Abstract Title: Lateralized prefrontal current-stimulation effects during verbal working memory high-load maintenance
  
 Abstract:
 Lateralized prefrontal current-stimulation effects during verbal working memory high-load maintenance. Meiron, Oded(1); Lavidor, Michal(1,2) 1 The Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel 2 Department of Psychology, University of Hull, UK Background and aims: Cognition enhancing effects have been sporadically observed in humans receiving transcranial direct current stimulation (tDCS) over the prefrontal cortex (Frengi et al., 2005, Jo et al., 2009). Specifically, recent findings demonstrated that on-line left dorsolateral prefrontal (DLPFC) anodal stimulation may improve working memory (WM) performance compared to sham stimulation of the same area (Andrews et al., 2011). We investigated a specific prefrontal verbal WM mechanism, executive attention, and how its function may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. Method: We measured "online" WM performance (accuracy scores) while participants (N =41, 22 females) received active or sham (placebo) transcranial direct current stimulation, and implicit learning performance (cued recall accuracy) in a post-stimulation WM task. Online WM and implicit learning performance was assessed using a verbal n-Back task (10 min long). Results: Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Conclusions: We believe that our findings support the possibility of using brain stimulation to enhance WM in neurological and psychiatric populations, as well as demonstrating novel gender-specific properties related to executive attention, a critical prefrontal core-mechanism of working memory capacity.
Abstract ID: 8
First Name: Jalal
Last Name: Solati
Abstract Title: PRENATAL EXPOSURE TO BACTERIAL LPS LEADS TO LONG-LASTING PHYSIOLOGICAL CONSEQUENCES IN MALE OFFSPRING
  
 Abstract:
 PRENATAL EXPOSURE TO BACTERIAL LPS LEADS TO LONG-LASTING PHYSIOLOGICAL CONSEQUENCES IN MALE OFFSPRING. Solati, J. ; Asiaei, M. Department of Biology, Faculty of Science, Karaj Branch, Islamic Azad University, Karaj, Iran. Growing evidence suggests that early life events are critical determinants for disorders later in life. According to a comprehensive number of epidemiological/animal studies, exposure to lipopolysaccharide, causes alteration in pro-inflammatory cytokine levels, hypothalamicpituitaryadrenal functioning and the hormonal system which may contribute to behavioral and neurological injuries. In this study we investigated the effects of lipopolysaccharide administration on physiological parameters in pregnant dams and their male offspring aged 9 weeks. In gestational Day 10, pregnant mice were injected intrapritoneally with Salmonella enterica lipopolysaccharide to model prenatal exposure to infection. The following results were obtained for offspring from dams stressed during pregnancy: (a) reduced anxiety-related behavior in the elevated plus maze; (b) reduced food and water intake; (c) reduced body weight from birth up to postnatal Day 40. The observed data provide experimental evidence showing that prenatal stress can have complex and long-lasting physiological/behavioral consequences in offspring.
Abstract ID: 9
First Name: Cittoor Girija
Last Name: Navaneedhan
Abstract Title: HOW METAPHORICAL THINKING INFLUENCES BRAIN CHEMISTRY AND LEARNING
  
 Abstract:
 How metaphorical thinking influences Brain Chemistry and learning Author Dr (Mrs) Cittoor Girija Navaneedhan Associate Professor Rajalakshmi College of Education Thandalam Chennai Email id: girija60@rediffmail.com Abstract Brain Chemistry is closely associated with learning as it sets a systematic co-ordination between millions of neurons to form complex web-like signaling systems that represent a state which is a combination of emotional, cognitive and physical interactions helping an individual to make decisions. If the learner is conditioned to this state of mind he/she would be able to orchestrate the mind signaling that would optimize their learning. Achieving this state of mind could be possible by utilizing one of the natural characters of the brain is by relating two different universes in their meaning often referred as Metaphorical thinking. Establishment of this state of mind at conscious and sub conscious level promotes continuity and flexibility in the signaling system, otherwise considered as hard wired brain being a seat for primary emotions such as joy, fear, anger, disgust, surprise and sadness. Several research studies have proved that brain is naturally designed to allow most of the learning disappears from memory, it is necessary to ensure explicit learning and memory state governed by the Hippocampus of the brain. Hippocampus has a small capacity which could be easily overloaded but by creating a systematic signaling system combining emotional, cognitive and physical interactions promoting the capacity of the Hippocampus. Practice of Metaphorical thinking in understanding given information promotes the communication of the two hemispheres by a bundle of connecting fibers, the corpus callosum at neo cortex level and through hippocampus at the level of limbic system. Hence, Metaphorical thinking helps learners to make connections and develop patterns and relationships in parallel to the language as well as symbols relevant to the given information. The present research work explores the link between Brain Chemistry and learning through Metaphorical thinking. Keywords: Metaphorical thinking, Hippocampus, learning and Systematic Signaling
Abstract ID: 11
First Name: Anthony
Last Name: Kline
Abstract Title: THE ATYPICAL ANTIPSYCHOTIC DRUG ARIPIPRAZOLE ENHANCES COGNITION AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY
  
 Abstract:
 THE ATYPICAL ANTIPSYCHOTIC DRUG ARIPIPRAZOLE ENHANCES COGNITION AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY. Phelps, T.I.; Cheng, J.P.; Kline, A.E.; Physical Medicine & Rehabilitation, Safar Center for Resuscitation Research, Center for Neuroscience, Center for the Neural Basis of Cognition, and Psychology, University of Pittsburgh, Pittsburgh, PA 15213 Background and aims: Antipsychotic drugs (APDs) are routinely administered after traumatic brain injury (TBI) to reduce agitation and aggression. However, APDs with dopamine2 (D2) receptor antagonist properties (e.g., haloperidol and risperidone) impede cognitive recovery after TBI. Therefore, evaluation of APDs with different mechanisms of action is warranted. Aripiprazole (ARIP) exhibits 5-HT1A and D2 receptor agonist activity, but not D2 antagonism. Studies from our laboratory have shown that pharmacological agents with these properties enhance outcome after TBI. Thus, the aim of the study was to test the hypothesis that ARIP will enhance motor and cognitive performance after TBI. Methods: Adult male rats were anesthetized and received either a cortical impact (2.8 mm depth) or sham injury and then received either ARIP (0.1, 0.5, or 1.0 mg/kg; i.p) or saline VEHicle beginning 24 hours after injury and once daily for 19 days. Motor (beam-balance/walk) and cognitive (Morris water maze) performance was assessed on post-operative days 1-5 and 14-19, respectively. Results: The Sham groups did not differ from one another and thus the data were pooled. No motor differences were revealed among the TBI+VEH and TBI+ARIP groups [p>0.05]. No cognitive differences were revealed among the TBI+VEH and the TBI+ARIP (0.5 and 1.0 mg/kg) groups [p=0.94 and p=0.43]. In contrast, the TBI+ARIP (0.1 mg/kg) group performed better in the water maze vs. the TBI+VEH group [p=0.0036] and did not differ from the SHAM controls [p>0.05]. Conclusions: No deleterious effects on behavioral outcome were observed with ARIP after TBI. Furthermore, the lower dose of ARIP facilitated spatial learning. The findings support our hypothesis and suggest that 1) ARIP may be a safer alternative for alleviating behavioral disturbances in TBI patients, and 2) may be effective in improving cognitive function. Future studies will explore specific mechanism(s) mediating the beneficial effects of ARIP on recovery after TBI.
Abstract ID: 12
First Name: Armando
Last Name: Ferreira-Nuño
Abstract Title: THE MULTIPLE PARTNER CHOICE ARENA SATISFIES THE CONSTRUCT VALIDITY OF AN ANIMAL MODEL TO STUDY PREMETURE EJACULATION
  
 Abstract:
 THE MULTIPLE PARTNER CHOICE ARENA SATISFIES THE CONSTRUCT VALIDITY OF AN ANIMAL MODEL TO STUDY PREMETURE EJACULATION. Ferreira-Nuo A., Olayo-Lortia J, Cruz-Benites A, Velzquez-Moctezuma J, Morales-Otal A. Dpto. Biologa de la Reproduccin. Universidad Autnoma Metropolitana - Iztapalapa. Mxico D.F. 09340. fena@xanum.uam.mx. Premature ejaculation (PE) is a frequent male sexual complaint. According to Waldinger (2005), this sexual disorder is mediated mainly by disturbances of serotonergic neurotransmission and certain serotonin (5-HT) receptors. In the actual animal model (AM) to study PE, once the male sexual behavior (MSB) of a rat is obtained in a Standard Arena (SA, a closed cylinder), the male receives a chronic administration of a drug to test later if the treatment could prolong their ejaculation latency. This AM satisfies the construct and predictive validity criteria, but not the face validity, because the male rat do not behaves as PE from the beginning. Recently we develop a new AM to study PE: the Multiple Partner Choice Arena (MPCA) made with four acrylic cylinders placed together in a cross fashion and each with a small hole in the bottom directed to the central area. A sexually expert male rat is placed in each cylinder and a receptive female located in the central area is allowed choose the male who wants to copulate with. Under the competitive conditions imposed by the MPCA all the males behave as PE, satisfying the face validity criteria of an AM. To demonstrate if the MPCA also satisfies the construct validity of an AM, 0.1mg/kg of WAY 100635 (a 5-HT1A receptor antagonist) in 0.03 ml of saline was administered during 15 consecutive days to 14 male rats (WAY Group) while the CONTROL group (CON Group, n =14) only received the saline. During days 1, 8 and 15 of the treatment MSB was registered in the SA in half of the males of each group and the other half was tested in the MPCA. The chronic administration of WAY 100635 could abolish the PE behavior as significant reductions in mount, intromission and ejaculation latencies and intromission frequency observed in the CON group tested in the MPCA disappear in the WAY Group. Then MPCA could satisfy the construct criteria of an animal model.
Abstract ID: 13
First Name: Jodi
Last Name: Lukkes
Abstract Title: EFFECTS OF ADOLESCENT SOCIAL ISOLATION ON TRYPTOPHAN HYDROXYLASE-2 MRNA EXPRESSION IN THE DORSAL RAPHE NUCLEUS OF ADULT FEMALE RATS.
  
 Abstract:
 EFFECTS OF ADOLESCENT SOCIAL ISOLATION ON TRYPTOPHAN HYDROXYLASE-2 MRNA EXPRESSION IN THE DORSAL RAPHE NUCLEUS OF ADULT FEMALE RATS. 1Lukkes, J.L.; 1Kopelman, J.M.; 1Donner, N.C.; 1, 2Hale, M.W.; 1Lowry, C.A. 1Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA. 2School of Psychological Science, La Trobe University, Melbourne, VIC 3086, Australia Adverse early life experience is thought to increase an individuals susceptibility to mental health disorders, including anxiety disorders and depression, later in life. Our previous studies have shown that post-weaning social isolation of female rats during a critical period of development sensitizes an anxiety-related serotonergic dorsal raphe nucleus (DR)-basolateral amygdala circuit in adulthood. Therefore, we investigated the effects of post-weaning social isolation of female rats on anxiety-like behavior in a social interaction test. In addition, we also examined how post-weaning social isolation, in combination with a challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142), affects anxiety-like behavior in the home cage and tryptophan hydroxylase 2 ( tph2) mRNA expression in the DR of female rats using in situ hybridization histochemistry. Juvenile female rats were reared in isolation or groups of three for a 3-week period from weaning (postnatal day (P) 21 to mid-adolescence (P42), after which all rats were group-reared for an additional 2 weeks until adulthood. Isolation-reared rats exhibited increased anxiety-like behavior in their home cage following administration of FG-7142 compared to group-reared rats. However, no treatment differences were observed in the social interaction test. No effects of isolation-rearing were observed on tph2 expression in the DR. However, we found that FG-7142 decreased tph2 mRNA expression in both isolates and group-reared rats. These results confirm that adolescent social isolation increases anxiety-like behavior during adulthood in female rats and indicate a possible novel mechanism whereby FG-7142 affects tph2 gene expression. Supported by: NIMH F32MH084463 (JLL) and R01MH086539 (CAL).
Abstract ID: 14
First Name: Katharina
Last Name: Hillerer
Abstract Title: HIPPOCAMPAL NEUROGENESIS IS DIFFERENTIALLY REGULATED UNDER BASAL AND CHRONIC STRESS CONDITIONS IN MALE AND FEMALE RATS
  
 Abstract:
 HIPPOCAMPAL NEUROGENESIS IS DIFFERENTIALLY REGULATED UNDER BASAL AND CHRONIC STRESS CONDITIONS IN MALE AND FEMALE RATS. Hillerer K.M.1; Neumann I.D.1; Couillard-Despres S.2; Aigner L.2; Slattery D.A.1 1 Department of Molecular and Behavioural Neuroendocrinology. University of Regensburg, Germany 2 Department of Molecular Regenerative Medicine. Paracelsus Medical Private University Salzburg, Austria. Sex differences in both basal and stress-induced hippocampal neurogenesis processes have been reported in the literature. However, studies directly comparing basal and stress-induced sex differences on multiple neurogenesis processes are lacking to date. Therefore, the aim of the present study was to directly compare cell proliferation and survival, neuronal and astroglial differentiation and stem cells quiescence in males and females under both basal and chronic stress conditions (12 days of 2 h RS). In addition, CORT levels and spatial working memory were assessed. Under basal conditions, only the number of immature neurons was different between males and females. In contrast, chronic stress resulted in a number of sex-specific alterations. Thus, stress exposure reduced cell proliferation in males, which was reflected by an increase in stem cell quiescence, while it did not alter either parameter in females. In contrast, stress exposure decreased cell survival in females only. Analysis of astroglial and neuronal differentiation patterns revealed that chronic stress specifically diminished the number of mature neurons in females, with no effect in males. Despite the observed sex differences in adult hippocampal neurogenesis, spatial working memory was unchanged in either sex. Basal CORT levels were higher in females, whereas exposure to chronic stress did not affect basal plasma CORT levels in either sex across the stress period. This is the first direct comparison of sex-dependent and chronic stress-induced changes in adult hippocampal neurogenesis, which will lead to a better understanding of sex differences in neurogenesis processes.
Abstract ID: 15
First Name: Erik
Last Name: Oleson
Abstract Title: SUBSECOND MESOLIMBIC DOPAMINE RELEASE PREDICTS THE AVOIDANCE OF PUNISHMENT
  
 Abstract:
 SUBSECOND MESOLIMBIC DOPAMINE RELEASE PREDICTS THE AVOIDANCE OF PUNISHMENT Erik B. Oleson, Ronny N. Gentry and Joseph F. Cheer Department of Anatomy and Neurobiology. University of Maryland School of Medicine. Baltimore, MD 21201 USA. The mesolimbic dopamine system is generally considered to be a reward pathway. In support of this theory – when animals are presented with conditioned cues predicting reward availability, midbrain dopamine neurons fire in high frequency bursts. This pattern of neural activity results in subsecond dopamine release events in terminal fields such as the nucleus accumbens, which are thought to promote reward seeking. A number of studies, however, also implicate the mesolimbic dopamine system in behavior requiring the avoidance of punishment. To assess the role of dopamine during the avoidance of punishment, we measured accumbal dopamine concentrations in near real-time using fast-scan cyclic voltammetry while well-trained rats responded in an operant signaled shock avoidance task. In this procedure, a stimulus light was presented as a warning signal while a response lever extended 2s prior to the delivery of recurring foot shocks (0.5s shock every 2s). A lever response at any time within the session produced a 20s safety period signaled by a tone. This design allowed us to assess dopamine signaling during warning signal presentation, safety periods and two distinct behavioral responses (avoidance and escape). We found that dopamine release encodes warning signal presentation and predicts when animals will successfully avoid punishment. Our data, demonstrating that dopamine indiscriminately processes motivationally salient stimuli, supports a growing consensus that the mesolimbic dopamine system is more than merely a reward pathway. Rather, subsecond dopamine signaling might facilitate behavioral orientation in a manner that promotes behavioral adaptation and survival.
Abstract ID: 16
First Name: Lena
Last Name: Elkman
Abstract Title: INVESTIGATION OF THE REWARDING EFFECTS OF MORPHINE WHEN CO-ADMINISTERED WITH FLUPIRTINE
  
 Abstract:
 INVESTIGATION OF THE REWARDING EFFECTS OF MORPHINE WHEN CO-ADMINISTERED WITH FLUPIRTINE. Elkman, L; Broadbear, J; Goodchild, C; Kolosov, A. School of Psychology and Psychiatry, Monash University, Australia. Whilst the opioid drug morphine is effective for treating many pain states, its analgesic benefits are coupled with troublesome addictive properties that make it liable to abuse. A promising approach for improving the utility and reducing the abuse liability of opioids is to use lower doses of opioids, in combination with non-opioid analgesics, thus maintaining an optimal level of analgesia with reduced adverse effects. Recent studies in both humans and rats have demonstrated that the use of morphine in conjunction with the non-opioid analgesic flupirtine, may be effective in treating chronic pain states. The aim of the present study was to examine the reinforcing effects of morphine and flupirtine, in order to examine their abuse potential when given alone and in combination. 140 male Wistar rats were evaluated in the well validated rodent model of Conditioned Place Preference (CPP), in which they learned to associate a distinctive environment with the effects experienced following drug treatment, and to associate a different environment with the absence of the drug. The results of this study showed that intraperitoneally administered morphine produced CPP at two doses (4 and 8mg/kg). Flupirtine (10 and 20mg/kg) did not cause significant CPP, suggesting that the non-opioid has a low abuse potential. Co-administration of morphine and flupirtine did not result in any significant CPP, with the addition of flupirtine appearing to reduce morphine CPP. This study provides preliminary evidence that combinations of low-dose morphine and the non-opioid analgesic flupirtine, which have been found to have potent analgesic effects, may have a lower abuse potential than the use of analgesic doses of morphine alone. Abuse of prescription opioid medications is a major health problem in the first world. The development and utilization of combination analgesics containing flupirtine and low-dose morphine may be an effective strategy for reducing the potential for opioid abuse.
Abstract ID: 17
First Name: Jee Hyun
Last Name: Kim
Abstract Title: Contextual influence in conditioned fear in juvenile rats: forgetting vs. extinction
  
 Abstract:
 The most common way of studying learned fear in the laboratory involves a Pavlovian conditioning procedure in which an initially neutral conditioned stimulus (CS) is presented with an aversive unconditioned stimulus (US). Subsequent presentations of the CS elicit a variety of fear behaviors. These fear responses can be spontaneously forgotten over time, at least due to changes in the context from where the memory is acquired. Alternatively, fear is also reduced by repeatedly presenting the CS without the US. This procedure is referred to as extinction. Extinction has attracted much attention over the past decade (for review, see Kim & Richardson, 2010), because understanding how fear is diminished is critically important to the development of effective treatments for various anxiety disorders. Similar to spontaneous forgetting, it is widely accepted that extinction memory is context-specific, at least in adult rats. That is, any changes in temporal, physical, or internal context from where extinction training has occurred can bring back the fear memory without any re-training (i.e., spontaneous recovery, renewal and reinstatement). However, I have collected substantial behavioral and neurobiological evidence that show fundamental differences in the extinction processes across development. Specifically, postnatal day (P) 17 rats (infant/juvenile), in contrast to P24 rats (pre-adolescent), fail to show spontaneous recovery, renewal or reinstatement following extinction of learned fear, suggesting that extinction is context-independent and is effectively erasure in P17 rats. These differences are accompanied by developmental differences in the neural circuitry underlying extinction, as indicated by immunohistochemistry and localized infusion studies. Interestingly, spontaneous forgetting in P17 rats appears to be sensitive to contextual influences, which suggests a double dissociation between forgetting and extinction across development. These findings suggest novel ways to explore treatments for anxiety disorders, and highlight that treatments should focus on the young population.
Abstract ID: 18
First Name: Joshua
Last Name: Ward
Abstract Title: EXPOSURE TO NON-OLFACTORY RECEPTOR-MEDIATED CUES RESULTS IN FACIAL SIMILARITY RECOGNITION THAT IS CORRELATED WITH HUMAN LEUKOCYTE ANTIGEN GENOTYPES.
  
 Abstract:
 EXPOSURE TO NON-OLFACTORY RECEPTOR-MEDIATED CUES RESULTS IN FACIAL SIMILARITY RECOGNITION THAT IS CORRELATED WITH HUMAN LEUKOCYTE ANTIGEN GENOTYPES. Ward, J.M.; Vallender, E.J.; Knapp, L.A. Division of Neuroscience, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA. The genes in the major histocompatibility complex, known in humans as the human leukocyte antigen (HLA), are extraordinarily diverse and have roles in immune recognition and susceptibility to infectious and autoimmune diseases. While the high degree of HLA polymorphism is driven in large part by natural selection via pathogen co-evolution, increasingly it has also been investigated for a role in kin recognition. However, a steady reliance on olfactory cues for the past twenty-four years has produced a one dimensional perspective on how HLA-mediated behavior is manifested, often resulting in controversy over researchers inability to replicate results. Acknowledging that human perception is the manifestation of numerous cues, this study aimed to identify a non-olfactory receptor-mediated cue that affects human perception in order to facilitate HLA-mediated behavior. A visual cue, facial similarity, was tested by presenting standardized photographs of related and non-related females to a survey group. Female perception of facial similarity was demonstrated to be both significantly perceivable amongst those surveyed and participants were able to pair others who share more HLA alleles together based on facial similarity. Results suggest support for the hypothesis that HLA genes may play a role in human kin recognition. Moreover, these findings implicate non-olfactory receptor-mediated cues as a signal for HLA-mediated behavior, suggesting HLA-associated olfactory receptors may not be the exclusive driver of HLA-mediated behavior. Further work aims to determine the physiological mechanism behind non-olfactory receptor-mediated HLA-associated behavior.
Abstract ID: 19
First Name: Catherine
Last Name: Barrett
Abstract Title: RESILIENCE TO EARLY LIFE STRESS IN FEMALE PRAIRIE VOLES (MICROTUS OCHROGASTER): POTENTIAL MODERATION BY OXYTOCIN RECEPTORS.
  
 Abstract:
 RESILIENCE TO EARLY LIFE STRESS IN FEMALE PRAIRIE VOLES (MICROTUS OCHROGASTER): POTENTIAL MODERATION BY OXYTOCIN RECEPTORS. Barrett, C.E.; Modi, M.;Young, L.J. Ctr. Transl. Soc. Neurosci. Yerkes Primate Ctr. Emory Univ., Atlanta, GA, 30329, USA. We examined effects of stress during the postnatal period on adult attachment in the highly social, monogamous prairie vole. Between PND1-14 litters underwent daily 3hr social isolations, and adult offspring were assessed for partner preference formation. Neonatally isolated females did not display a partner preference after 48 hrs of cohabitation while controls did (F1,18=5.33,p=0.033). To explore the neural mechanisms underlying this disruption in females, we quantified oxytocin receptor (OTR) density in the nucleus accumbens (NAcc), which is critical for partner preference formation. Early social isolation did not alter NAcc OTR expression. However, isolated females with low levels of NAcc OTR did not display a preference for their mated partner, while those with high OTR densities did (F1,16=8.11,p=0.012). In isolated females, but not controls, time spent huddling with the partner correlated strongly with oxytocin receptor binding in the nucleus accumbens (R=0.66,R2=0.43,p<0.05). This potential gene by environment interaction suggests that females with low OTR levels in the NAcc may have a heightened susceptibility to disruptions in social development. We also present findings that postnatal treatment during the first week of life with an MC4 receptor agonist, which activates oxytocin neurons, enhances adult social bonding in female voles (F1,32=4.87,p=0.035). The role of oxytocin in the neonatal environment may be critical in the development of social neural circuits. Future studies will examine the potential of neonatal oxytocin enhancements in buffering against adverse early events.
Abstract ID: 20
First Name: Andrew
Last Name: Novick
Abstract Title: EFFECTS OF ADOLESCENT SOCIAL DEFEAT ON COGNITION AND PREFRONTAL CORTEX DOPAMINE FUNCTION
  
 Abstract:
 EFFECTS OF ADOLESCENT SOCIAL DEFEAT ON COGNITION AND PREFRONTAL CORTEX DOPAMINE FUNCTION. Novick, A.M.; Forster, G.L.; Watt, M.J. Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion SD 57069 USA. Bullying victimization during adolescence is associated with an increased incidence of psychiatric disorders characterized by deficits in executive function. These often manifest as impairments in working memory, the ability to utilize and maintain task-relevant information. We have shown that adolescent male rats exposed to social defeat stress, a model of human bullying, develop persistent reductions in prefrontal cortex dopamine (PFC DA) activity. Given the known role of PFC DA in mediating executive function, we hypothesized that PFC DA hypofunction caused by adolescent social defeat would result in decreased working memory in early adulthood. Rats were exposed daily to repeated social defeat from postnatal day (P) 35-39, with age-matched controls placed into empty cages for the duration of each defeat trial. At P56, subjects were trained in one of two working memory tasks. Compared to controls, rats defeated in adolescence exhibited impaired performance both in the delayed win-shift task when a 5 min delay was used, and in the delayed alternating T-maze test with a 90 s delay. To further investigate mechanisms underlying altered PFC DA activity and related behaviors following adolescent defeat, quantitative autoradiography was used to identify potential differences in markers of DA function. Previously defeated rats showed upregulation of the DA transporter, which may contribute to decreased DA availability within the PFC and subsequent deficits in working memory. Combined, findings suggest that cognitive deficits associated with bullying victimization may be a direct result of psychosocial stress-induced insult to the developing adolescent PFC DA system. Support: NIH P20 RR15567, NIDA RO1 DA019921, and USD Joseph F. and Margaret P. Nelson Grant.
Abstract ID: 21
First Name: Vanessa
Last Name: Janowski
Abstract Title: DISPLAY AND SEARCH DYNAMICS IN MULTI-ATTRIBUTE CHOICE
  
 Abstract:
 Display and search dynamics in multi-attribute choice. Vanessa Janowski, Erik Madsen, Martjin Willemsen, Eric Johnson, Antonio Rangel. Consumer choices are a crucial component of everyday decisions. When entering a store to make a purchase, consumers are confronted with shelves full of items and must quickly parse and select among a variety of options. Understanding the details of this decision-making process is therefore essential for developing models of choice behavior. We hypothesized that (1) while display configuration would not have a significant impact on search, (2) search patterns would impact choice through value integration. We tested these hypotheses using a two-item, two-attribute choice task to determine how decision-making processes are modified by the introduction of multiple discrete attributes for each item. Subjects were presented with pairs of posters, each of a different design and size, and asked to choose the more desirable one. Attributes of each choice were arranged in two visual conditions: designs on top, and sizes on top. Mouselab was used to gather detailed search-process data. Choices were then compared to prior value measures to construct psychometric choice curves. We found striking differences in search patterns depending on the condition, which subsequently impacted choice through differential weighting and integration of the attributes. Our results have important implications for product attribute emphasis and placement.
Abstract ID: 22
First Name: Kelsy
Last Name: Ervin
Abstract Title: RAPID EFFECTS OF ESTROGEN RECEPTOR AGONISTS ON SOCIAL TRANSMISSION OF FOOD PREFERENCES IN FEMALE MICE
  
 Abstract:
 RAPID EFFECTS OF ESTROGEN RECEPTOR AGONISTS ON SOCIAL TRANSMISSION OF FOOD PREFERENCES IN FEMALE MICE. Ervin, K.; Friesen, J.; Gallagher, N.; Roussel, V.; Zicherman, J.; Clipperton Allen, A.; Phan, A.; Choleris, E. Dept. of Psychology. University of Guelph, Guelph, ON N1G 2W1 Canada. The social transmission of food preferences (STFP) is a specifically social learning paradigm in which an animal exhibits a preference for a novel food based on olfactory cues provided by a conspecific. Estrogens can modulate performance on this task. In mice, estrogen receptor alpha (ER-alpha) agonists eliminate the preference for the demonstrated food, whereas estrogen receptor beta (ER-beta) agonists prolong the preference (Clipperton et al., 2008). In these studies, STFP was assessed 48 hours after drug administration. This time scale points at long-term effects of estrogen. Estrogens are also known to have behavioural effects within minutes of treatment. On this rapid time scale, ER-alpha agonists improve social recognition and increase dendritic spine density in the hippocampus, while ER-beta agonists impair social recognition (Phan et al., 2011). Whether social learning would also be affected in a similarly rapid time scale is currently unknown. We therefore administered 17beta-estradiol, the ER-alpha agonist propyl pyrazole triol (PPT), and the ER-beta agonist diarylpropionitrile (DPN) to ovariectomized observer mice 15 minutes prior to brief social exposure to a recently fed demonstrator mouse. We used a modified STFP paradigm that allowed us to examine the effect on the acquisition phase of STFP, with specific attention to the first hour of testing for possible rapid effects. Results show that within this first hour, 17beta-estradiol improves performance. These results extend the rapid effects of estrogens to a social learning paradigm and shows that estrogenic effects on learning of socially acquired information can be much more rapid than previously thought.
Abstract ID: 23
First Name: Alaine
Last Name: Keebaugh
Abstract Title: OXYTOCIN RECEPTOR KNOCKDOWN PRAIRIE VOLES DISPLAY SOCIAL DEFICITS AND PROVIDE NOVEL MODELS FOR THE SCREENING OF PHARMACOTHERAPUTICS
  
 Abstract:
 OXYTOCIN RECEPTOR KNOCKDOWN PRAIRIE VOLES DISPLAY SOCIAL DEFICITS AND PROVIDE NOVEL MODELS FOR THE SCREENING OF PHARMACOTHERAPUTICS. Alaine C. Keebaugh1, Catherine E. Barrett1, Jasmine J. Jenkins1,2 and Larry J. Young1 1Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA 2Behavioral Research Advancements in Neuroscience (BRAIN) Fellow, Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA, USA Studies have implicated oxytocin and its receptor (OXTR) in the mediation of social behaviors, and disruptions in this system have been linked to diseases of social deficits such as autism spectrum disorder (ASD). Recently, Oxtr knockout mice have been shown to model multiple components of the ASD phenotype. We extend these studies by site-specifically manipulating this gene in the socially monogamous prairie vole. Here, we use viral-mediated RNA interference (RNAi) to generate knockdown of Oxtr within the shell of the nucleus accumbens (NAcc) of prepubertal female prairie voles. This localized gene knockdown blocked the formation of a pair bond, and resulted in reduced spontaneous nurturing behavior and maternal care. Currently we are extending our behavioral phenotyping to explore the role of accumbal OXTR signaling in the occurrence ASD related behaviors such as cognitive stereotypy and communication. We are complementing these studies by testing the ability of pharmacotherapuetics to rescue pair bond formation. These results underscore the potential of using viral-mediated RNAi for the rapid production and testing of genetic disease models in this species and for identifying pharmacotherapeutics for diseases of social deficits such as ASD.
Abstract ID: 24
First Name: Mitsuhiro
Last Name: Yoshimura
Abstract Title: CISPLATIN-INDUCED ANOREXIA IS ATTENUATED BY RIKKUNSHITOU, A TRADITIONAL JAPANESE HERBAL MEDICINE (KAMPO) IN RATS.
  
 Abstract:
 CISPLATIN-INDUCED ANOREXIA IS ATTENUATED BY RIKKUNSHITOU, A TRADITIONAL JAPANESE HERBAL MEDICINE (KAMPO) IN RATS. Yoshimura, M.; Funada, M.; Hayashi, T.; Ohkubo, J.; Katoh, A.; Ohno, M.; Ishikura, T.; Hashimoto, H.; Kakuma, T.*; Yoshimatsu, H.*; Terawaki, K.**; Uezono, Y.**; Ueta, Y. Dept. of Physiology, School of Medicine, Univ. of Occupational and Environmental Health, Kitakyushu 807-8555, Japan. *Dept. of Internal Medicine 1, School of Medicine, Oita Univ. Oita 879-5503, Japan. **Division of Cancer Pathophisiology, Group for Development of Molecular diagnostics and Individualized Therapy, National Cancer Center Research Institute, Tokyo 104-0045, Japan. Rikkunshitou (RKT), a traditional Japanese herbal medicine (Kampo), has been widely prescribed to improve anorexia in Japan. However, the efficacy and the mechanism of its action are exactly unknown. Here we studied whether RKT could improve anorexia induced by cisplatin (Cis) in rats. Adult male rats were divided into 4 groups; water + saline (WS), water + Cis (WC), RKT + saline (RS) and RKT + Cis (RC). Water or RKT (0.1 g/kg) was administered per os (p.o) by probe one time per day on evening for 7 days, then saline or Cis (6 mg/kg) was administered intraperitoneally (i.p). After i.p administration of saline or Cis, cumulative food intake, water intake and body weight were measured for 3 days. Plasma glucose levels were measured 3 days after i.p administration. In the 3-day measurements, there were no significant changes in cumulative water intake. Although the body weight and cumulative food intake of RC was not as same as that of WS, it increased compared to that of WC 3 days after i.p administration. In addition, decreased plasma glucose levels due to Cis-induced anorexia in WC recovered as well as that of WS in RC. These results suggest that RKT may be therapeutic potential for anorexia induced by Cis.
Abstract ID: 25
First Name: Nathan
Last Name: Marchant
Abstract Title: CONTEXT-INDUCED RELAPSE TO ALCOHOL SEEKING AFTER PUNISHMENT IN A RAT MODEL
  
 Abstract:
 CONTEXT-INDUCED RELAPSE TO ALCOHOL SEEKING AFTER PUNISHMENT IN A RAT MODEL. Marchant, N. J.; Khuc, T. N.; Bonci, A.; Shaham, Y. Behavioral Neuroscience Research Branch, NIDA, Baltimore, MD, USA. Rationale and objective: Many studies have demonstrated context-induced reinstatement of alcohol seeking after its suppression by extinction of the alcohol-reinforced responding. However, it is unknown whether contexts can provoke relapse to alcohol seeking that is suppressed by punishment. This is an important question because abstinence in humans typically occurs because of the increasing negative consequences associated with excessive alcohol use. Methods: Two groups of alcohol-preferring P rats were given 12 24-hr sessions of home cage intermittent access to 20% ethanol. Next, they were trained every other day in 2-h sessions to self-administer 20% ethanol (0.1 ml/reward delivery) in one context (context A); the final reinforcement schedule was VI30. Subsequently, all rats continued to self-administer alcohol in the punishment context (context B). For one group, 50% of alcohol deliveries were punished by footshock (0.4-0.9 mA, 0.5-s) for 3-7 sessions until alcohol-reinforced responding less than 20 responses; the other group received no shocks. All rats were then tested for alcohol seeking in 30-min extinction tests in both contexts. Results: We found that alcohol seeking recovered on test in context A. In contrast, alcohol seeking remained suppressed on test in context B. Interestingly, responding in context A on test did not differ between groups Punished and Unpunished. Conclusions: Our data indicate that the effect of punishment on alcohol seeking is context specific. We propose that the punishment-context relapse model can be used to explore mechanisms of relapse after conditions that more closely mimic abstinence promotion in humans.
Abstract ID: 26
First Name: Jeffrey
Last Name: Barr
Abstract Title: CHRONIC AMPHETAMINE TREATMENT ALTERS MECHANISMS OF SEROTONIN UPTAKE IN THE RAT VENTRAL HIPPOCAMPUS
  
 Abstract:
 CHRONIC AMPHETAMINE TREATMENT ALTERS MECHANISMS OF SEROTONIN UPTAKE IN THE RAT VENTRAL HIPPOCAMPUS 1,4Barr, J.L.,1Scholl,J.L., 3Lowry,C.A.,2Renner,K.J.,1 Watt, M.J., and 1Forster, G.L. 1Basic Biomedical Sciences and Neuroscience Group, 2Department of Biology and Neuroscience Group, Sanford School of Medicine, The University of South Dakota, Vermillion, SD; 3Department of Integrative Physiology and Center for Neuroscience, University of Colorado-Boulder, Boulder, CO; 4Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA Serotonergic neurotransmission within the hippocampus is necessary for stress adaptation, and the ventral hippocampus is associated with affective behavior in rats. We have shown that rats undergoing amphetamine withdrawal exhibit increased anxiety-like behavior and diminished serotonergic activity in the rat ventral hippocampus. We tested the hypothesis that reduced serotonergic activity during amphetamine withdrawal is a result of alterations to serotonin re-uptake. using in vivo microdialysis in anesthetized adult male Sprague Dawley rats. Chronic pretreatment with amphetamine (2.5 mg/kg, i.p.; 14 days) did not affect serotonin accumulation induced by local application of the selective serotonin uptake inhibitor paroxetine in the ventral hippocampus. However, blockade of the polyspecific organic cation transporter via decynium-22 produced a dose-dependent increase in extracellular serotonin in the ventral hippocampus of control rats that was significantly attenuated in rats pretreated with amphetamine. Protein expression of the serotonin transporter was unaltered, whereas the organic cation transporter 3 was increased in the ventral hippocampus following amphetamine administration. These results suggest chronic amphetamine administration diminishes the availability of extracellular serotonin in the ventral hippocampus via increased organic cation transporter 3-mediated uptake of serotonin. This in turn, may result in increased anxiety states observed during amphetamine withdrawal. Supported by: NIH grant R01 DA019921.
Abstract ID: 27
First Name: Jordy
Last Name: van Enkhuizen
Abstract Title: IMPAIRED ATTENTION OF DOPAMINE TRANSPORTER (DAT) KNOCKDOWN (KD) MICE IN A CONTINUOUS PERFORMANCE TEST: SIMILARITIES TO PATIENTS WITH BIPOLAR DISORDER (BD)
  
 Abstract:
 IMPAIRED ATTENTION OF DOPAMINE TRANSPORTER (DAT) KNOCKDOWN (KD) MICE IN A CONTINUOUS PERFORMANCE TEST: SIMILARITIES TO PATIENTS WITH BIPOLAR DISORDER (BD). van Enkhuizen, J.1,2; Geyer, M.A.1,3; Young, J.W.1. 1UCSD, La Jolla, CA, USA; 2Utrecht University, Utrecht, Netherlands; 3VA, VISN 22, La Jolla, CA, USA. Impaired attention is apparent in several neuropsychiatric disorders including BD. The continuous performance test (CPT) is widely used to assess attention in humans using target and non-target stimuli. We have described DAT KD mice as a model of BD. To further validate this model, we trained wildtype (WT; n=28) and DAT KD (n=31) mice in the 5-choice serial reaction time task (5CSRTT) and the 5-choice CPT (5C)-CPT. We hypothesized that DAT KD mice would be hyper-responsive in the 5CSRTT but exhibit impaired response control in the 5C-CPT. For the 5CSRTT, mice were trained to holepoke when a stimulus (target) appeared in 1 of 5 locations. The 5C-CPT included non-target stimuli with 5 locations illuminated, requiring inhibition from responding. During initial training in the 5CSRTT, DAT KD mice made more premature responses compared with WT mice (F(1,57)=25.7, p<0.001), although levels normalized over time. Once stable in the 5CSRTT, DAT KD mice omitted fewer trials than WT mice (F(1,57)=7.0, p<0.05). When in the 5C-CPT however (requiring the inhibition of responding), omission levels of DAT KD mice became comparable to WT mice but the former responded more often to non-target stimuli (T=-2.2, p<0.05). With training, WT and DAT KD mice improved their response inhibition to non-target stimuli, but the difference between the two genotypes remained. Mice with reduced DAT expression exhibited hyper-responding in the 5CSRTT as measured by increased premature responses and fewer omissions. When discriminated responding was required by introducing non-target stimuli however, DAT KD mice exhibited difficulty inhibiting from responding while their omissions normalized. Thus, DAT KD mice exhibit impaired attention consistent with BD patients.
Abstract ID: 28
First Name: Matthew
Last Name: May
Abstract Title: Cat Cheek Rubbings Elicit Defensive Behavior In Rats
  
 Abstract:

Cat Cheek Rubbings Elicit Defensive Behavior In Rats

Matthew May *, Michael T. Bowen **, Iain S. McGregor **, William Timberlake *

* The Department of Psychological and Brain Sciences, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405, United States.

** School of Psychology, University of Sydney, NSW 2006, Australia.

Abstract (294 words) Laboratory rats display pronounced defensive behaviors when confronted with a range of cat-derived stimuli, including collars worn by a cat, cloths rubbed on a cat, and cat fur. One possible explanation of this phenomenon (the kairomone hypothesis) is that rats derive a survival advantage by eavesdropping on signals used by cats to communicate with each other. Cats are known to rub their cheeks on objects at strategic environmental locations to signal their identity, territory and mating potential to other cats. The current study assessed the sensitivity of laboratory rats to these cheek markings. In Experiment 1, food deprived Sprague Dawley rats were trained to consume food pellets in one arm of a Y maze. On test day a damp cloth was placed near the food pellets that had been rubbed on a location (wall) where a cat had recently engaged in cheek rubbing. A control cloth and a worn cat collar were also tested. Both the cat collar and cheek rubbing residue were effective in increasing the latency to eat and the amount of food eaten. Disruption of consummatory behavior in the test environment was also evident 24 h later in the absence of the odor stimulus. Experiment 2 tested the reaction of Wistar rats to cheek rubbings using a paradigm in which rats were given the opportunity to hide. Rats exposed to a cotton pad that had been wiped at a cat cheek rubbing location (door) showed increased hiding behavior, decreased exploration and reduced stimulus approach and contact. Conditioned defensive responses persisted in these rats for up to four days following stimulus exposure. These results suggest that rats eavesdrop readily on the cheek rubbings that cats use to mark their territory and provide further support for the kairomone hypothesis of predator odor avoidance. Enter SuperScript text here
Abstract ID: 29
First Name: Nina
Last Name: Donner
Abstract Title: INESCAPABLE TAIL SHOCK AND COLD SWIM STRESS INTERACT TO ELEVATE TPH2 MRNA EXPRESSION IN AN ANXIETY-RELATED SUBSET OF SEROTONERGIC NEURONS.
  
 Abstract:
 INESCAPABLE TAIL SHOCK AND COLD SWIM STRESS INTERACT TO ELEVATE TPH2 MRNA EXPRESSION IN AN ANXIETY-RELATED SUBSET OF SEROTONERGIC NEURONS. 1Donner, N.C.; 2Kubala, K.H.; 3Drugan, R.C.; 2Maier, S.F.; 1Lowry, C.A. Depts. of 1Integrative Physiology, 2Psychology & 1,2Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA. 3Dept. of Psychology, University of New Hampshire, NH, USA. The effects of stressful stimuli on the expression of tryptophan hydroxylase 2 (tph2) mRNA expression are controversial. The tph2 gene encodes the rate-limiting enzyme for serotonin synthesis. Here, we studied the effects of inescapable tail shock (IS; 100 5 s, 1.0 mA shocks with random intervals), cold swim stress (SWIM; 10 min, 15 C), or the succession of IS and SWIM on tph2 mRNA expression in the dorsal raphe nucleus (DR), using in situ hybridization histochemistry. Adult male rats served as home cage controls (HC, n=8), or were exposed to IS (n=8) or SWIM (n=8), and were killed 4 h after the start of either stressor. Another group of rats was exposed to IS on day 1, and either HC (n=8) or SWIM (n=8) on day 2, with all rats being killed 4 h after the start of SWIM. IS, but not SWIM, was sufficient to increase tph2 expression selectively in the anxiety-related dorso-caudal DR (cDRD). Furthermore, IS on day 1 sensitized rats to SWIM-induced increases of tph2 expression in the cDRD and to increases in the ratio of plasma interleukin-6 to interleukin-10 on day 2. Compared to HC-SWIM control rats, the IS-SWIM group also displayed increased immobility and decreased climbing behavior in the SWIM test. Our results indicate that stressor type and severity are crucial factors in regulating tph2 expression, and that IS creates a neuronal, immunological, and behavioral vulnerability to a succeeding stressor.
Abstract ID: 30
First Name: Gerald Jr.
Last Name: Deehan
Abstract Title: THE ROLE OF THE BASOLATERAL AMYGDALA IN CONDITIONED CUE-INDUCED ALTERATIONS IN ALCOHOL-SEEKING
  
 Abstract:
 The Role of the Basolateral Amygdala in Conditioned Cue-Induced Alterations in Alcohol-Seeking G.A. Deehan Jr.; S. R. Hauser; E.A. Engleman; Z-M. Ding; W.J. McBride; Z.A. Rodd. Indiana University School of Medicine, Dept. of Psychiatry, Indianapolis IN, 46202. Exposure to stimuli (conditioned cues) previously associated with drug availability can elicit drug-seeking behaviors thereby increasing the likelihood of drug relapse. Conditioned cues can be positively (CS+) or negatively (CS-) associated with the availability of a reinforcer and neurobiological data indicate that presentation of a CS+, associated with alcohol (EtOH) access, increased c-Fos+ neurons in the basolateral amygdala (BLA). Therefore, the current experiments examined the effects of the pharmacological silencing of the BLA (GABA agents) on conditioned cue-induced EtOH-seeking and the effect of conditioned cue presentation on glutamate (GLU) levels in the BLA. Alcohol-preferring (P) rats were trained to self-administer EtOH in an operant chamber in which a CS+ or CS- signaled the availability or absence of EtOH respectively. A CS0 was presented in neutral environment with no association to EtOH access. Pharmacological silencing of the BLA was effective at blocking the ability of the CS+ to enhance EtOH-seeking, but failed to prevent the expression of EtOH-seeking or the ability of the CS- to reduce EtOH-seeking. Microdialysis data indicated that presentation of the CS- decreased, while presentation of the CS+ increased, GLU levels in the BLA. The CS0 did not significantly alter GLU levels in the BLA. Overall, the data suggest that the BLA can mediate the effects of conditioned cues on drug-seeking, but not the expression of drug-seeking, and that alterations in GLU signaling in the BLA may represent an underlying neurological mechanism contributing to drug craving and relapse.
Abstract ID: 31
First Name: Nitish
Last Name: Mittal
Abstract Title: DO ARRESTINS ALTER THE EFFECTS OF DRUGS OF ABUSE THROUGH A COMMON TARGET?
  
 Abstract:
 DO ARRESTINS ALTER THE EFFECTS OF DRUGS OF ABUSE THROUGH A COMMON TARGET? Mittal, N. and Walwyn, W. Semel Instituse of Neuroscience and Human Behavior, University of California Los Angeles Although psycho-stimulants such as cocaine, and opiates, such as morphine, bind with different targets, the rewarding and addictive properties of these drugs are mediated through a common mechanism, long-term functional adaptations of the dopaminergic system. As arrestins, widely-expressed scaffolding proteins, modulate the function of both opioid and dopamine receptors, we have examined the effect of deleting either of the non-visual arrestins, (-arrestin 1 or 2) on psychomotor sensitization and the rewarding properties of cocaine or morphine. Removing -arrestin 1 does not alter the acquisition of cocaine-seeking behaviors or the resultant psychomotor sensitization but does affect the persistence of cocaine seeking, a phenotype reminiscent of GluR1 deletion in dopamine neurons. In contrast, mice lacking -arrestin 1 do not show morphine reward, and while the total psychomotor sensitization to repeated morphine is unchanged, the contribution of the delta opioid receptor is absent. Removing -arrestin 2 does not affect the addiction profile of cocaine. However, we have found both reduced hyperlocomotor and rewarding effects of morphine in mice lacking -arrestin 2. The reduced locomotor effects of morphine in these mice are due to altered JNK activity suggesting a novel role of this stress-activated kinase in modulating the addictive properties of this opiate. These data suggest that arrestin modulation of the psychomotor and rewarding properties of cocaine or morphine may not occur through a common final mechanism, but rather reflect specific and varied roles of the arrestins in the development of addiction to these drugs.
Abstract ID: 32
First Name: Jeff
Last Name: Grimm
Abstract Title: RELATIVELY BRIEF EXPOSURE TO AN ENRICHED ENVIRONMENT EFFECTIVELY BLOCKS SUCROSE SEEKING AND REDUCES SUCROSE SELF-ADMINISTRATION IN RATS
  
 Abstract:
 RELATIVELY BRIEF EXPOSURE TO AN ENRICHED ENVIRONMENT EFFECTIVELY BLOCKS SUCROSE SEEKING AND REDUCES SUCROSE SELF-ADMINISTRATION IN RATS. Grimm J.W.; Weber R.; Barnes J.; Koerber J.; Dorsey K.; Deuse L.; Glueck E.; Collins S.; North K. Department of Psychology and Program in Behavioral Neuroscience. Western Washington University. Environmental enrichment dramatically reduces drug and sucrose seeking in rats. In a previous study we reported that 1 month of environmental enrichment (large cage, toys, and social cohorts) effectively blocked cue-induced sucrose seeking. In the present study, we examined whether overnight (22h) enrichment would be as effective. We also examined whether social enrichment (housing with a conspecific only) might account for the environmental enrichment effect. Rats self-administered 10% sucrose (.4 mL/delivery) in daily 2-h sessions wherein each sucrose delivery was accompanied by a tone+light cue. Sucrose seeking was measured after either 1 or 30 days of forced abstinence in a session identical to training but no sucrose was delivered with the cue. In the 22 h preceding, rats either remained singly-housed (control), were housed with another rat in a double-wide cage (social enrichment), or were housed with 2 other rats plus toys in a large habitat (environmental enrichment). Both enrichment conditions markedly reduced sucrose seeking after 1 day of forced abstinence. Sucrose consumption was also reduced in a next-day test. Both enrichment conditions also reduced sucrose seeking when administered after 1 month of forced abstinence, but environmental enrichment was approximately two and a half times as effective as social enrichment. Self-administration in a next-day test was reduced only in the environmentally-enriched rats. These are the first results we are aware of indicating that a relatively brief exposure to environmental enrichment can nearly abolish sucrose seeking and decrease sucrose self-administration. Social enrichment does not completely account for this effect. Preliminary results with pretreatment of rats immediately prior to enrichment with the corticosterone antagonist mifepristone (20 mg/kg IP) indicate that HPA activation is not responsible for the effects of either social or environmental enrichment.
Abstract ID: 33
First Name: Anna
Last Name: Phan
Abstract Title: THE NATURE OF HIPPOCAMPAL INVOLVEMENT IN ESTROGEN-MEDIATED LEARNING ENHANCEMENT
  
 Abstract:
 THE NATURE OF HIPPOCAMPAL INVOLVEMENT IN ESTROGEN-MEDIATED LEARNING ENHANCEMENT

Phan A, Suschkov S, Pecchioli N, Seguin L, Winters BD, Choleris E

Dept of Psychology, University of Guelph, ON, Canada.

Previously, we reported systemic administration of physiological doses of 17β-estradiol rapidly (within 40min) enhanced learning (object placement, object recognition, social recognition), likely via action at ERα (Phan et al., 2011). Estrogen also rapidly increased dendritic spine density in the CA1 hippocampus, suggesting a site of action of estradiol rapid effects on learning. Therefore, bilateral microinjections of 17β-estradiol (25nM, 50nM, and 100nM) into the hippocampus of young adult ovariectomized female CD1 mice were performed 15min prior to testing in object placement, object recognition and social recognition paradigms. We found that intrahippocampal 50nM of 17β-estradiol improved performance on all 3 learning paradigms. Thus, the hippocampus seems capable of mediating 17β-estradiols rapid facilitatory effects on social and object recognition as well as object location learning. The results with the object placement paradigm are consistent with the established involvement of the hippocampus in spatial and contextual learning. However, its role in object and social recognition is unclear. Lesions of the hippocampus do not consistently impair object or social recognition. One possibility is that the hippocampus is not necessary for, but may facilitate, social and object recognition by providing spatial contextual information. Therefore, we tested the effects of intrahippocampal infusions of 17β-estradiol on object or social recognition when mice were tested in a Y-apparatus, which minimizes spatial and contextual cues. In the Y-apparatus intrahippocampal 17β-estradiol improved object recognition, but not social recognition. Therefore, while estradiol action in the hippocampus may directly facilitate learning and memory about objects, it may only indirectly facilitate social recognition, by providing contextual information. Funded by NSERC.

Abstract ID: 34
First Name: Michael
Last Name: Bowen
Abstract Title: DEFENSIVE AGGREGATION (HUDDLING) IN LABORATORY RATS IN RESPONSE TO PREDATOR ODORS: GENERAL CHARACTERISTICS AND NEURAL CORRELATES
  
 Abstract:
 DEFENSIVE AGGREGATION (HUDDLING) IN LABORATORY RATS IN RESPONSE TO PREDATOR ODORS: GENERAL CHARACTERISTICS AND NEURAL CORRELATES. Bowen, M.T.; Kevin, R.; Kendig, M.D. ; McGregor, I.S. School of Psychology, University of Sydney, NSW 2006 Australia. Rats show characteristic defensive responses to predator odors, such as hiding, avoidance, risk assessment, and inhibition of non-defensive behaviors. While these species-typical responses have been extensively examined in individual rats in the laboratory, the response of groups of rats has rarely been studied. In a series of recent experiments we have found that groups of 4 Wistar rats exposed to a ball of cat fur in a large test arena show pronounced defensive aggregation (huddling), spending long periods in tight clumps of 3 or 4 rats at maximal distance from the odor source. Group size is an important determinant of huddling, with groups of four, but not two, familiar rats huddling. Many groups were found to consist of 1-2 active responders that approach the cat odor source more readily, and 2-3 passive responders who spend nearly all of their time huddling. The traits of these individuals remain remarkably stable over repeated trials with cat fur although coping style in the cat odor paradigm did not necessarily predict coping style on other models of anxiety. Fos immunohistochemistry showed that, compared to rats exposed to cat odor alone, those exposed to cat fur in a group had: less activation in the lateral amygdala, LPO, medial caudoputamen, dorsomedial PAG and lateral habenula; and more activation in the mitral cell layer of the AOB. Compared to rats with more passive coping styles, those with more active coping styles had: less activation in the lateral AON, accumbens shell, ventrolateral septum and barrel cortex; and more activation in the mitral cell layer of the AOB. Finally, blockade of vasopressin V1a receptors by administration of the V1a receptor antagonist SR 49059 (1 mg/kg IP) interfered with defensive aggregation, suggesting that, as in songbirds and zebrafish, V1a receptor stimulation plays an important role in defensive aggregation in rats.
Abstract ID: 37
First Name: Maria Chiara
Last Name: PIERI
Abstract Title: THE USE OF AGOMELATINA IN DRUG ADDICTED PATIENTS WITH PSYCHIATRICS DISORDERS
  
 Abstract:
 THE USE OF AGOMELATINA IN DRUG ADDICTED PATIENTS WITH PSYCHIATRICS,Dept of Mental Health and Drug Dependebce Bologna East;Pieri,M.C.;Comaschi,A.C. Agomelatine is an antidepressant drug that has a type melatoninergic agonist action on receptors MT1 and MT2, and an antagonistic action on receptor 5HT/20. Agomelatine has no interactions with the reuptake of monoamines and has no affinity for alpha receptors Beta-adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine, We have selected, by the total number of patients treated for heroin, cocaine, alcohol dependence at the SerT East Bologna, a group of 28 patients We observed this group during a period of 6 months using Ham A, Ham D, VAS craving substances, VAS for sleep, Quality of Life and the number of hours for the sleep and the sensation of the patient for the sleep ( sleep was good or bad ?) Agomelatine is the first; in a class of melatoninergic drugs that could be very important in the treatment of sleep disorder, anxiety and mood in patients, in particular, with dependence heroin in opioid agonist treatment but also in other dependence Patients improve the quality of your life and improve the number of hour slept and we can see a decrease of use heroin, cocaine and alcohol 2 abstracts The effects of the agonist therapy in anxious-depressed positive HCV drug-abusers treated with IFN therapy; Dept of Mental Health and Drug Dependebce Bologna East;Pieri,M.C.;Comaschi,A.C. Addiction present three stage: social use , regulated relapse and compulsive relapse and the abuse of drugs and the stressful events are able to activate CREB determining an increase in the gene transcription of dynorphins with the consequent increase in the activity of the kappa receptors-mediated. The important general clinical objectives in addiction are To Induce a stable abstinence condition To Prevent or to treat co-morbidity situations To Promote and maintain a global Quality of Life and satisfactory state of health Buprenorphine , in base to k-receptor antagonism, modify the emotional disregulation ,that often appears with depressive symptoms, dysphoria and anxiety as soon as after the use of the first dose of opioids. The block of k receptors allows to buprenorphine to decrease these effects. The normalitation of the stress axis operated by buprenorphine contribuites to its stabilizing action on the psycho-physical effect. Hcv decreases the mood and a re-balancing with agonist drugs improves also the quality of life We choose , in the group of patients treated in east drug addiction unit with agonist of opioid and HCV hepatitis, 44 patients: 30 patients taking buprenorphine (68%) ; 14 patients taking metadone (32%) . We divided the patients into 3 subgroups: 1)Patients taking buprenorphine and SSRI ( escitalopram) 2)Patients taking matadone and SSRI ( escitalopram) 3) Patients taking buprenorphine The occupation is an important factor for the success of the treatment All the three subgroups successfully ended the treatment with INF keeping the depression under control.only with buprenorphine or in association with SSRI
Abstract ID: 38
First Name: Neeraj
Last Name: Kumar
Abstract Title: EFFECT OF RADIOFREQUENCY ELECTROMAGNETIC RADIATION THROUGH GLOBAL SYSTEM OF MOBILE COMMUNICATION - 900 MHZ ON LOCOMOTOR ACTIVITY OF RATS
  
 Abstract:
 EFFECT OF RADIOFREQUENCY ELECTROMAGNETIC RADIATION THROUGH GLOBAL SYSTEM OF MOBILE COMMUNICATION - 900 MHZ ON LOCOMOTOR ACTIVITY OF RATS.Kumar, N.; Khan, R.A.; Sharma, V.P.; Khan, M.Y.Babasaheb Bhimrao Ambedkar University, Lucknow-226025, UP, India & CSIR - Indian Institute of Toxicology Research, Lucknow - 226001, UP, India. The increasing tendency of GSM mobile phone (MP) usage among the younger users especially children and adolescents have led to assess the behaviour implications. MP radiates an average power of 0.2-0.6 watts and near 40-50 percent phone energy absorbed into the brain. The aim of our study was to investigate the effects of EMR from GSM mobile phone on Spontaneous Locomotor Activity of rats. Wister albino rats were grouped in control and EMR and placed in circular cell phone exposure (CCPE) cage. CCPE cage was specially designed for EMR exposure to rats by MP in the laboratory condition and these cages were placed in absence of other electric appliances in experimental room. MP was placed in centre and rats were allowed to move around the device within 10 cm. radius area. EMR group were exposed for 3 hours/day (7 days in week) by MP. Spontaneous locomotor activity in rats was carried out using computerized Actimot (TSE, Germany) following the method of Ali et al. (1990). We found a decrease in total distance travelled (12 %), time moving (23%), rearing (25%) and an increase in resting time (10%) as compared to rats in the control group. Simultaneous without GSM-900MHz EMR from MP in rats increased the total distance travelled (9%), time moving (4%) and rearing (6%) and decreased the resting time (1%) as compared to rats exposed with GSM-900MHz EMR. Although distance travelled, time moving and rearing decreased in the sham group compared with controls; these parameters remained decreased as compared to sham group. Study concluded that 3 hours/day acute exposure of EMR (900MHz) through MP could not alter the locomotor activity of rats. We acknowledge to Uttar Pradesh Council of Science and Technology, Lucknow for providing the grant for this study.
Abstract ID: 39
First Name: Eimeira
Last Name: Padilla
Abstract Title: EFFECTS OF DIFFERENT HALLUCINOGENIC NMDA ANTAGONISTS AND XYLAZINE ON FEAR EXTINCTION
  
 Abstract:
 Effects of different hallucinogenic NMDA antagonists and xylazine on fear extinction. Eimeira Padilla, John DeMis, Dong-Oh Seo, DeAnna Adkins and Marie H. Monfils. Department of Psychology, The University of Texas at Austin, USA.Ketamine and phencyclidine (PCP) are NMDA antagonists with hallucinogenic properties. Recently, ketamine has been used to treat patients with treatment-resistant depression (Ibrahim et al., 2011, Messer et al., 2010). However, peritrauma ketamine administration can also produce sustained posttraumatic stress symptoms following a traumatic experience (Schnenberg et. al., 2005, Winter and Irle 2004). Given the high co-morbidity of depression and anxiety-related disorders (DeVane et al., 2005), administration of ketamine may exacerbate trauma-linked memories. The present study examines the long-term effects of NMDA antagonists on the extinction of traumatic memories. In animals and humans, ketamine is usually given in combination with a sedative (e.g. xylazine in animals) for anesthesia. Thus, we examined the long-term effects of ketamine plus xylazine, ketamine alone, xylazine or PCP alone on later fear extinction in rats. Rats were fear conditioned by pairing a tone with a footshock. One day after fear conditioning, they received systemic injections of ketamine plus xylazine, ketamine, PCP, xylazine or vehicle. The rats then received an extinction session either 1-day or 1-week following drug injection. Ketamine plus xylazine impaired fear extinction (i.e. more freezing behavior) compared to vehicle in the 1-day and 1-week extinction groups. Ketamine alone impaired fear extinction in the 1-day extinction group. There were no effects of PCP or xylazine alone on fear extinction. The current study provides evidence that a single injection of ketamine impairs fear extinction 24 hours later and a long-term impairment is observed with the addition of xylazine, a potent sedative. The goal of ongoing studies is to identify the behavioral and neural mechanisms underlying short-term and long-term retrieval and extinction of fear memories that have been reinforced with ketamine.
Abstract ID: 41
First Name: PANOS
Last Name: ZANOS
Abstract Title: PERSISTEN UP-REGULATION OF THE VASOPRESSIN V1a RECEPTOR FOLLOWING CHRONIC MORPHINE AND COCAINE ADMINISTRATION IN THE BRAIN
  
 Abstract:
 PERSISTEN UP-REGULATION OF THE VASOPRESSIN V1a RECEPTOR FOLLOWING CHRONIC MORPHINE AND COCAINE ADMINISTRATION IN THE BRAIN
Zanos, P.; Winsky-Sommerer, R.; Kitchen, I; Bailey, A.
Faculty of Health and Medical Sciences, University of Surrey, GU27XH, U.K.

Recent findings suggested a key role for arginine vasopressin (AVP) in the modulation of drug seeking and withdrawal. The present study aims to investigate the effect of chronic morphine and cocaine treatment on the central vasopressinergic system. For both morphine and cocaine studies, male C57BL/6J mice were separated into five groups (n=6). For the morphine study mice were treated with a 7-day saline or escalating dose morphine administration paradigm (2 x 20-100mg/kg/day i.p.), or withdrawn for a period of either 1 or 7 days. For the cocaine study, mice were treated with a saline or 14-day escalating dose cocaine administration paradigm (3 x 15-30mg/kg/day i.p.), or withdrawn for a period of either 1 or 14 days. Quantitative autoradiographic brain mapping of the vasopressin V1a and V1b receptors was performed using [3H]AVP. To discriminate between V1aR and V1bR, SSR149,514 (specific V1bR antagonist) was used. In both experiments, a significant effect of treatment (p<0.001), region (p<0.001) and treatment x region interaction (p<0.01) was observed (2-way ANOVA). Both chronic cocaine and morphine administration significantly increased V1aR binding within the amygdala, nucleus accumbens, piriform cortex, and lateral septum (p<0.05). This up-regulation persisted following acute and chronic withdrawal when V1aR binding was also significantly up-regulated in the hypothalamus (p<0.01). No detectable V1bR binding sites were observed in the brain regions analyzed. These results indicate a prolonged activation of the V1aR after chronic cocaine and morphine administration within brain regions associated with behavioural responses, reward and stress. These data suggest that alteration of the V1aR may be a neurobiological mechanism involved in the pathophysiology of opioid and cocaine addiction and relapse.

Abstract ID: 42
First Name: Juliana
Last Name: Kroon
Abstract Title: THE ROLE OF DORSAL AND VENTRAL HIPPOCAMPUS IN THE ACQUISITION, STRENGTHENING AND EXPRESSION OF OLFACTORY FEAR CONDITIONING IN RATS
  
 Abstract:
 THE ROLE OF DORSAL AND VENTRAL HIPPOCAMPUS IN THE ACQUISITION, STRENGTHENING AND EXPRESSION OF OLFACTORY FEAR CONDITIONING IN RATS. Kroon, J.A.V.; Carobrez, A.P. Departamento de Farmacologia. UFSC, Florianopolis, Brazil. The association between an odor and an aversive event is an effective model to study the neurobiology of associative fear memories. Several studies revealed differential contributions for the dorsal and ventral portions of hippocampus (HPC) in cognition and emotion processes. The present work was outlined to evaluate the role of NMDA receptors in the ventral and dorsal HPC on the generation, strengthening and expression of aversive memories of rats submitted to the Olfactory Fear Conditioning (OFC) paradigm. The acquisition phase occurred in a conditioning chamber where subjects received 5-footshock-pairings associated with amyl acetate odor (CS; conditioned stimulus). The expression of conditioned emotional responses (CER) occurred in an odor box where the CS was exposed. Male Wistar rats bilaterally implanted with guide cannulae aimed at the ventral (HPCv) or the dorsal (HPCd) HPC were injected with NMDA receptor antagonist (AP5 6 or 24nmol) or NMDA receptor agonist (NMDA100 or 200pmol) or PBS before/after the conditioning or pre-CS test session. In Experiment 1, AP5 into the HPCd, pre-conditioning session, reduced the CER toward CS when compared to the PBS-group. In Experiment 2, AP5 either into the HPCd or the HPCv, pre-CS test, reduced CER toward CS. In experiment 3, NMDA into the HPCd, immediately after a weak training paradigm (1footshock+odor), promoted OFC, while PBS or NMDA-only (no-shock) failed. These results suggest that the acquisition and strengthening of fear memory requires the participation of HPCd NMDA receptors. Moreover, the expression of fear requires the activation of NMDA receptors from both HPCd and HPCv.
Abstract ID: 43
First Name: Milena
Last Name: Viana
Abstract Title: ACUTE RESTRAINT DIFFERENTLY ALTERS DEFENSIVE RESPONSES AND FOS IMMUNOREACTIVITY IN THE RAT BRAIN
  
 Abstract:
 ACUTE RESTRAINT DIFFERENTLY ALTERS DEFENSIVE RESPONSES AND FOS IMMUNOREACTIVITY IN THE RAT BRAIN. Andrade, JS; Abrao, RO; Cespedes, IC; Garcia, MC; Nascimento, JOG; Spadari-Bratfisch, RC; Melo, LL; da Silva, RB; Viana, MB. Dept. of Biosciences. Federal University of Sao Paulo (UNIFESP), Santos, SP 11060001 Brazil. Results from a previous study shows that rats exposed to acute restraint display anxiogenic-like behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. In contrast, escape responses were unaltered by stress exposure. Since ETM avoidance and escape tasks seem to activate distinct sets of brain structures, it is possible that the differences observed with acute restraint are due to particularities in the neurobiological mechanisms which modulate these responses. In the present study, analysis of fos protein immunoreactivity (fos-ir) was used to map areas activated by exposure of male Wistar rats to restraint stress (30 min) previously (30 min) to the ETM. Corticosterone levels were also measured in stressed and non-stressed animals. Confirming previous observations restraint facilitated avoidance performance, an anxiogenic result, while leaving escape unaltered. Performance of avoidance task increased fos-ir in the frontal cortex, intermediate lateral septum, anterior hypothalamus and dorsal raphe nucleus. In contrast, performance of escape increased fos-ir in the basolateral amygdala, ventromedial hypothalamus, dorsolateral periaqueductal gray and locus coeruleus. Both behavioral tasks also increased fos-ir in the dorsomedial hypothalamus. Restriction significantly raised corticosterone levels. Additionally after restriction, fos-ir was predominantly seen in the dorsal raphe of animals submitted to the avoidance task. This data confirms that different sets of brain structures are activated by ETM avoidance and escape tasks and suggests that acute restraint differently alters ETM behavior and the pattern of fos activation in the brain.
Abstract ID: 44
First Name: Craig
Last Name: Motbey
Abstract Title: ANALYSIS BY AUTORADIOGRAPHY FOLLOWING MEPHEDRONE (4-METHYLMETHCATHINONE) INDUCED SELF ADMINISTRATION BEHAVIOUR IN ADOLESCENT RATS.
  
 Abstract:
 Analysis By Autoradiography Following Mephedrone (4-Methylmethcathinone) Induced Self Administration Behaviour In Adolescent Rats. Craig P. Motbey1, Nadine Apetz1, Paul D. Callaghan2, Kelly Clemens3, Jennifer Cornish3, Iain S. McGregor1. Mephedrone (4-methylmethcathinone, MMC) is a novel recreational drug that has rapidly increased in popularity in recent years. In this study, we compared MMC-driven self-administration behaviour in male adolescent Sprague-Dawley rats with the well-characterised stimulant methamphetamine (METH). A variety of doses and schedules were used in order to develop dose-response curves for both fixed- and progressive-ratio reward schedules before a final stage of maximum-dosage drug access. During this final period, MMC rats self-administered a mean of 31.3 mg/kg/day MMC, while METH rats self-administered a mean of 4 mg/kg/day METH. Three days after the completion of dosing, brains were analysed using OX-42 immunohistochemistry and FluoroJade-C fluorescence microscopy. In addition, autoradiographic analyses measured potential changes in levels of serotonin and dopamine transporters (SERT, DAT) as well as the inflammation marker TSPO. MMC was found to promote extremely vigorous self administration behaviour. Mean response levels for MMC under progressive ratio testing more than doubled those found for METH, with the most strongly responding animals continuing to work for MMC until the response/reward ratio passed 400. To the best of the authors knowledge, this rate of responding exceeds that found with any other drug of abuse. Under an FR1 schedule, peak responding for MMC was found at a dose of 0.1 mg/kg/infusion, while the highest response rate for METH was found at a dose of 0.01 mg/kg/infusion. During the progressive ratio test, MMC responding peaked at 1 mg/kg/infusion while the METH response was greatest at 0.3 mg/kg/infusion. All treatment groups tolerated dosage without mortality or apparent morbidity, although MMC animals gained less weight relative to other groups. No significant changes were observed on any of the neurological measures conducted. Although MMC does not appear to easily induce neurotoxicity, these findings suggest that MMC has an extremely high potential for inducing uncontrolled use and addiction. 1School of Psychology, University of Sydney 2Australian Nuclear Science and Technology Organisation 3Department of Psychology, Macquarie University
Abstract ID: 45
First Name: Laurence
Last Name: Coutellier
Abstract Title: IMPLICATION OF THE TRANSCRIPTION FACTOR NPAS4 IN COGNITIVE AND SOCIAL FUNCTIONS
  
 Abstract:
 IMPLICATION OF THE TRANSCRIPTION FACTOR NPAS4 IN COGNITIVE AND SOCIAL FUNCTIONS. Coutellier L., Beraki S., Saw N.L., Shamloo M. Behavioral and Functional Neuroscience Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA. A deregulation of the excitatory-inhibitory balance has been associated with a variety of human neurological disorders such as schizophrenia or autism. Most scientific studies have focused on the molecular mechanisms underlying the regulation of excitatory synapses. However, less is known about the activity-dependent regulation of inhibitory synapses and its reference to nervous system disorders. Here we are studying the transcription factor Npas4, which has been shown to regulate the formation and maintenance of inhibitory neurons. We first found that Npas4 is highly expressed in the brain and more specifically in the cortex and limbic system. Then, using a Npas4 knockout (KO) mouse line, we demonstrated the importance of Npas4 in social and cognitive functions: Npas4-KO animals showed social avoidance toward an unfamiliar conspecific and aggressivity toward their WT littermates. They also displayed impaired pre-pulse inhibition, indicative of sensorimotor gating deficits. Finally, we observed that mice lacking Npas4 have hippocampal-dependent memory impairments as tested in the novel object recognition test and a place-reversal learning task. Altogether, these results demonstrate the importance of the inhibitory pathways in the expression of social behavior and cognitive functions. Studying further the transcription factor Npas4 might help obtaining a better understanding of neurological diseases characterized by an imbalance between inhibition and excitation such as autism or schizophrenia.
Abstract ID: 46
First Name: Eimeira
Last Name: Padilla
Abstract Title: BIPOLAR-DEPRESSIVE BEHAVIOR IN HOLTZMAN RATS
  
 Abstract:
 Bipolar II disorder is characterized by novelty hyper-reactivity (hypomania) and depressive episodes. Learned helplessness is a model of depression in which pre-exposure to inescapable electric shock prevents learning a subsequent escape response. Holtzman rats are a commercially available strain that is highly susceptible to learned helplessness (Padilla et al. 2009). It is unknown which characteristics at baseline can predict helpless behavior after exposure to inescapable stress. We determined behavioral predictors of helplessness using the novel and familiar open-field tests, sucrose consumption, and passive harm-avoidance tasks before learned helplessness training and testing. Increased activity in a novel environment, but not general activity or habituation, predicted susceptibility to learned helplessness. Novelty reactivity was the best predictor of helplessness susceptibility. However, differences in other measures were not observed. A possible explanation is that Holtzman rats are exhibiting a bipolar phenotype, since novelty seeking is more characteristic of bipolar depression (Janowsky et al., 1999). Furthermore, elevated harm avoidance is characteristic of unipolar depression (Janowsky et al., 1999). In conclusion, a subpopulation of Holtzman rats showed a bipolar-like pattern in that they experience excessive behavioral activation in response to novelty followed by excessive behavioral inhibition in response to uncontrollable stress.
Abstract ID: 47
First Name: Christian
Last Name: Mller
Abstract Title: CALMODULIN-DEPENDENT KINASES IN THE ACQUISITION AND EXPRESSION OF ADDICTION RELATED BEHAVIOUR IN MAN AND MICE
  
 Abstract:
 CALMODULIN-DEPENDENT KINASES IN THE ACQUISITION AND EXPRESSION OF ADDICTION RELATED BEHAVIOUR IN MAN AND MICE. Mller, C.P. Psychiatric University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen 91054, Germany. Systematic use as well as addiction of psychoactive substances requires the establishment of multiple memory systems. It was shown that addiction and normal memories share a number of anatomical, morphological and molecular substrates. At glutamate receptive neurons, Ca2+/Calmodulin dependent kinases (CaMKs) are important substrates for the intracellular Ca2+ activation. They are involved in the regulation of the functional plasticity of the synapse. In particular CaMKs with an autophosphorylation molecular memory control receptor phosphorylation, transcription and LTP/LTD and are crucial for normal learning and memory. Here we discuss latest evidence for the involvement of various CaMKs in addiction related behaviours. Pharmacological as well as recent genetic approaches in animal models as well as in human samples show a crucial role for CaMKs in the establishment and expression of addiction related behaviours for various abused drugs. These findings suggest CaMKs as potential targets for prevention and/or treatment of drug addiction.
Abstract ID: 48
First Name: Romana
Last Name: Slamberova
Abstract Title: DOES PRENATAL METHAMPHETAMINE EXPOSURE INDUCE CROSS-SENSITIZATION TO OTHER DRUGS IN ADULT MALE RATS?
  
 Abstract:
 DOES PRENATAL METHAMPHETAMINE EXPOSURE INDUCE CROSS-SENSITIZATION TO OTHER DRUGS IN ADULT MALE RATS? Slamberova R; Pometlova M; Schutova B; Hruba L; Deykun K. Charles University in Prague, Third Faculty of Medicine, Department of Normal, Pathological and Clinical Physiology, Prague, Czech Republic. Our recent studies demonstated that prenatal methamphetamine MA exposure makes adult rats more sensitive to acute injection of the same drug. Other studies show that abuse of one drug may increase sensitivity to abuse of another drug (cross-sensitization). The aim of the present study was to examine the cross-sensitization between prenatal MA exposure and challenge dose of other drugs. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring were divided to groups with challenge dose of the tested drug; (1) the same drug as prenatally (MA), (2) drugs with similar mechanism of action (amphetamine, cocaine and MDMA), and (3) drugs with different mechanism of action (morphine and cannabinoids). Behavior in unknown environment was examined in Laboras, and active drug-seeking behavior in the Conditioned place preference (CPP). In the Laboras, prenatal MA exposure induced sensitization and cross-sensitization only after administration of MA and amphetamine challenge dose, while animals with cocaine and morphine challenge displayed rather tolerance. The active drug-seeking behavior in the CPP was induced by MA and morphine regardless of prenatal drug exposure and by cocaine in controls but not in prenatally MA-exposed rats. While control rats after amphetamine challenge dose did not show drug-seeking behavior, the increase was apparent in prenatally MA-exposed rats suggesting cross-sensitization. MDMA and cannabinoids did not induce drug-seeking behavior or even decreased it. Thus, our data demonstrate that there are cross-effects between prenatal MA exposure and the challenge dose of other drug in adulthood, however, prenatally MA-exposed rats do not display higher drug-seeking behavior (with exception of amphetamine challenge) as we expected. Supported by: GACR 305/09/0126, 264706/SVV/2012, CSM 110
Abstract ID: 49
First Name: Jodi
Last Name: Lukkes
Abstract Title: EFFECTS OF ADOLESCENT SOCIAL ISOLATION ON TRYPTOPHAN HYDROXYLASE-2 MRNA EXPRESSION IN THE DORSAL RAPHE NUCLEUS OF ADULT FEMALE RATS
  
 Abstract:
 EFFECTS OF ADOLESCENT SOCIAL ISOLATION ON TRYPTOPHAN HYDROXYLASE-2 MRNA EXPRESSION IN THE DORSAL RAPHE NUCLEUS OF ADULT FEMALE RATS. 1Lukkes, J.L.; 1Kopelman, J.M.; 1Donner, N.C.; 1, 2Hale, M.W.; 1Lowry, C.A.. 1Department of Integrative Physiology and Center for Neuroscience, University of Colorado, Boulder, CO, USA. 2School of Psychological Science, La Trobe University, Melbourne, VIC 3086, Australia Adverse early life experience is thought to increase an individuals susceptibility to mental health disorders, including anxiety disorders and depression, later in life. Our previous studies have shown that post-weaning social isolation of female rats during a critical period of development sensitizes an anxiety-related serotonergic dorsal raphe nucleus (DR)-basolateral amygdala circuit in adulthood. Therefore, we investigated how post-weaning social isolation, in combination with a challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142), affects anxiety-like behavior in the home cage and tryptophan hydroxylase 2 mRNA(tph2) expression in the DR of female rats using in situ hybridization. Juvenile female rats were reared in isolation or groups of three for a 3-week period from weaning (postnatal day (P) 21 to mid-adolescence (P42)), after which all rats were group-reared for an additional 2 weeks until adulthood. Among vehicle-treated rats, isolation-reared rats had decreased tph2 mRNA expression in subdivisions of the DR. Isolation-reared rats, but not group-reared rats, responded to FG-7142 with increased duration of vigilance and arousal behaviors. Isolation-reared rats treated with FG-7142, relative to group-reared rats treated with FG-7142, exhibited less locomotion and rearing. In addition, FG-7142 decreased tph2 expression in the entire DR of group-reared rats but had no effect in isolation-reared rats. These data suggest that adolescent social isolation alters the effects of stress-related stimuli on behavior and serotonergic systems, which have been implicated in the pathophysiology of stress-related neuropsychiatric disorders. Support: F32MH084463 (JLL) and R01MH086539 (CAL) from the NIMH.
Abstract ID: 50
First Name: AKIKO
Last Name: KATO
Abstract Title: Oxytocin Synthesis in the Hypothalamus are Influenced by Fasting and Refeeding in the Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rats
  
 Abstract:
 Oxytocin Synthesis in the Hypothalamus are Influenced by Fasting and Refeeding in the Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rats

Katoh, A. ; Ishikura, T.; Yoshimura, M.; Ohkubo, J.; Onaka, T.; Suzuki, H.; Ueta, Y. Department of Physiology and Otorhynolaryngology, School of Medicine, University of Occupational and Environmental Health, 807-8555, Japan Department of Physiology, Jichi Medical School, 329-0498, Japan

We have generated oxytocin (OXT)-monomeric red fluorescent protein 1 (mRFP1) transgenic rats that express the OXT-mRFP1 fusion gene in the hypothalamus and the posterior pituitary. The mRFP1 fluorescence was observed in the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the internal layer of the median eminence (ME) and the posterior pituitary. Our previous study demonstrated that salt loading for 5 days caused a marked increase in the expression of the mRFP1 gene in the hypothalamus and that the response of the OXT-mRFP1 transgene to chronic salt loading was greatly exaggerated in comparison with that of the OXT gene in the SON and the PVN (Katoh et al., Endocrinology 2011). The present study demonstrated that fasting for 2 days caused a marked increase of mRFP1 fluorescence in the SON, the PVN and the ME, and after fasting for 2 days, refeeding for 2 days returned the mRFP1 fluorescence on the same extent as control levels. These results suggest that OXT may be involved in the regulation of feeding and metabolic status in rats.

Abstract ID: 51
First Name: Staci
Last Name: Bilbo
Abstract Title: PROGRAMMING INNATE IMMUNITY: IMPLICATIONS FOR NEURAL AND BEHAVIORAL DEVELOPMENT
  
 Abstract:
 PROGRAMMING INNATE IMMUNITY: IMPLICATIONS FOR NEURAL AND BEHAVIORAL DEVELOPMENT. Bilbo, S.D. Department of Psychology and Neuroscience, Duke University, Durham, NC 27708, USA. A wide variety of host (genetic), biological (e.g., infections), and environmental factors (e.g., pollutants & toxins) have been implicated in autism, yet its etiology remains unknown. The immune system is well characterized for its critical role in host defense. Far beyond this limited role however, there is mounting evidence for the vital role the immune system plays within the brain, in both normal, homeostatic processes (e.g., sleep, metabolism, memory), as well as in pathology, when the dysregulation of immune molecules may occur. This recognition is especially critical during brain development. Microglia and astrocytes, the primary immunocompetent cells of the CNS, are involved in every major aspect of brain development and function, including neurogenesis, synaptic formation and pruning. Cytokines such as tumor necrosis factor [TNF]α, interleukin [IL]-1β, and IL-6 are produced by glia within the developing and adult CNS, and are implicated in synaptic scaling, long-term potentiation, and neurogenesis. Importantly, cytokines are involved in both injury and repair, and the conditions underlying these distinct outcomes are under intense investigation and debate. Evidence from both animal and human studies implicates the immune system in a number of disorders with known or suspected developmental origins, including autism. This talk will focus on the evidence that infection during the perinatal period of life acts as a vulnerability factor for later-life alterations in cytokine production, and marked changes in cognitive and affective behaviors throughout the remainder of the lifespan, with a focus on the hypothesis that long-term changes in brain glial cell function may underlie such vulnerability.
Abstract ID: 52
First Name: Eimeira
Last Name: Padilla
Abstract Title: BIPOLAR-DEPRESSIVE BEHAVIOR IN HOLTZMAN RATS
  
 Abstract:
 Bipolar-depressive behavior in Holtzman rats. Padilla, E.; Shumake, J.; Auchter, A.; Barrett, D.; Gonzalez-Lima, F. Departments of Psychology and Pharmacology, The University of Texas at Austin. Bipolar II disorder is characterized by novelty hyper-reactivity (hypomania) and depressive episodes. Learned helplessness is a model of depression in which pre-exposure to inescapable electric shock prevents learning a subsequent escape response. Holtzman rats are a commercially available strain that is highly susceptible to learned helplessness (Padilla et al. 2009). It is unknown which characteristics at baseline can predict helpless behavior after exposure to inescapable stress. We determined behavioral predictors of helplessness using the novel and familiar open-field tests, sucrose consumption, and passive harm-avoidance tasks before learned helplessness training and testing. Increased activity in a novel environment, but not general activity or habituation, predicted susceptibility to learned helplessness. Novelty reactivity was the best predictor of helplessness susceptibility. However, differences in other measures were not observed. A possible explanation is that Holtzman rats are exhibiting a bipolar phenotype, since novelty seeking is more characteristic of bipolar depression (Janowsky et al., 1999). Furthermore, elevated harm avoidance is characteristic of unipolar depression (Janowsky et al., 1999). In conclusion, a subpopulation of Holtzman rats showed a bipolar-like pattern in that they experience excessive behavioral activation in response to novelty followed by excessive behavioral inhibition in response to uncontrollable stress.
Abstract ID: 53
First Name: Zuoxin
Last Name: Wang
Abstract Title: PREFRONTAL OXYTOCIN MEDIATES DRUG AND SOCIAL REWARD INTERACTION
  
 Abstract:
 Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form pair bonds after mating. This behavior is mediated by dopamine (DA) and oxytocin (OT) neurotransmission in mesocorticolimbic brain regions, including the nucleus accumbens (NAcc) and prefrontal cortex (PFC). Similarly, the rewarding effects of drugs of abuse are also mediated by these neurotransmitter systems. Our recent studies in the prairie vole have demonstrated that exposure to the psychostimulant, amphetamine (AMPH), impairs mating-induced pair bonding; pair-bonding experience decreases the rewarding properties of AMPH; and such behavioral interactions are regulated by NAcc DA via a receptor-specific mechanism. In a most recent study in female prairie voles, we found that an AMPH treatment paradigm known to inhibit pair bonding decreased oxytocin receptor (OTR) density in the PFC. As PFC OTR activation is essential for pair bonding, decreased OT neurotransmission may mediate the AMPH-impairment of pair bonding. This notion is supported by our data showing that intra-PFC OT infusions restored mating-induced pair bonding in AMPH-treated voles. AMPH treatment also decreased DA D2-type (D2R), but not D1-type (D1R), receptor density and increased extracellular levels of DA in the NAcc. Both of these changes increase the likelihood of NAcc D1R activation, which inhibits pair bond formation. Interestingly, intra-PFC OT infusion tended to decrease NAcc DA activity, suggesting that PFC OT may interact with NAcc DA to restore pair bonding in AMPH-treated voles. Collectively, these data demonstrate that alterations in OT and DA neurotransmission underlie the AMPH-impairment of pair bonding and suggest that it may be worthwhile to pursue pharmacotherapies targeting central OT to restore prosocial behaviors in the addicted. (Supported by NIDAR01-19627, NIDAK02-23048, & NIMHR01-58616 to ZW and NIDAF31-25570 to KY).
Abstract ID: 54
First Name: Tim
Last Name: Karl
Abstract Title: CANNABINOIDS: A RISK FACTOR FOR A NEUREGULIN 1 MOUSE MODEL OF SCHIZOPHRENIA?
  
 Abstract:
 CANNABINOIDS: A RISK FACTOR FOR A NEUREGULIN 1 MOUSE MODEL OF SCHIZOPHRENIA?

Karl T.1, Long L.1, Boucher A.2, McGregor I.2, Huang X.-F.3 and Arnold J.2

1Neuroscience Research Australia, Randwick, Australia
2University of Sydney, Australia
3University of Wollongong, Australia

Heavy cannabis consumption, particularly during adolescence, appears associated with an increased risk of developing schizophrenia (SZ) in susceptible individuals. However, cannabis is a mixture of cannabinoids, including the psychotomimetic cannabinoid receptor 1 (CB1) agonist Δ9-tetrahydrocannabinol (THC) and the potentially antipsychotic-like cannabidiol (CBD). To clarify the role of cannabinoids in the development of SZ, we investigated the effects of chronic CB1 stimulation (i.e. THC and CP 55,940 treatment) in adolescent/ adult mice mutant for the SZ candidate gene neuregulin 1 (i.e. Nrg1 HET). We also characterized the impact of adult CBD exposure in these mice.
Adolescent male Nrg1 HET mice and their wild type-like (WT) littermates received vehicle or THC (10 mg/kg i.p.; 21 days), whereas adult cohorts were treated with vehicle, CP 55,940 (0.4 mg/kg; 15 days) or CBD (1, 50, 100 mg/kg; 21 days). Mice (N = 10/cohort) were tested for SZ-related behaviours and accompanying changes to neuronal activity (i.e. Fos expression) or expression of SZ-relevant receptors.
Adolescent mice were equally sensitive to the locomotor suppressant effects of THC. Neither treatment nor genotype had any impact on prepulse inhibition. THC impaired cognition and suppressed social interaction in WT mice. However, Nrg1 mutants developed behavioural tolerance to chronic CB1 stimulation more readily than WTs. Exposure to CBD attenuated the hyperlocomotor activity and prepulse inhibition deficit observed in vehicle-treated Nrg1 HETs. Behavioural changes were linked to altered neuronal activity and receptor expression.
Nrg1 mutants appear less sensitive to effects of adolescent CB1 stimulation but more susceptible than WT mice in adulthood. Importantly, chronic CBD rescued partially some of the behavioural abnormalities of Nrg1 mice.

Abstract ID: 55
First Name: Nay Lui
Last Name: Saw
Abstract Title: ACTIVATION OF Β1-ADRENERGIC RECEPTOR AS A POTENTIAL MEMORY ENHANCEMENT STRATEGY IN NEURO COGNITIVE DISORDERS.
  
 Abstract:
 ACTIVATION OF 1-ADRENERGIC RECEPTOR AS A POTENTIAL MEMORY ENHANCEMENT STRATEGY IN NEURO COGNITIVE DISORDERS. Saw N.L., Coutellier L., Shamloo, M. Behavioral and Functional Neuroscience Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA. Neurodegenerative diseases such as Alzheimers disease (AD) are characterized by severe cognitive deficits. Yet, the underlying mechanisms and causes of these symptoms remain elusive and reliable therapeutic strategies are still missing. My laboratory goal is to better understand the underlying mechanisms of the cognitive impairments observed in AD using experimental models of AD. We hypothesize that a disturbance in noradrenergic signaling could be responsible for these cognitive impairments. To test this hypothesis, we studied the Thy1-hAPP(Lond/Swe+) mouse line model of AD. Similarly to patient affected by AD, the Thy1-hAPP (Lond/Swe+) mouse line is characterized by a neurodegeneration of the locus coeruleus, primary source of noradrenergic innervations to various cortical areas. Furthermore this line displays social recognition deficit and cognitive deficits when compared to their wild-type littermates. We have shown that activation of a β1- adrenoreceptor (β1-ADR) by an agonist could rescue the cognitive and social deficit observed in this model. In conclusion, the disturbances in the neurotransmission regulated by the β1ADR might be responsible for some of the cognitive deficits observed in AD and β1ADR could be a potential therapeutic target for AD.
Abstract ID: 56
First Name: Kikuchi
Last Name: Yoshiaki
Abstract Title: NEURAL BASIS OF MATERNAL LOVE
  
 Abstract:
 NEURAL BASIS OF MATERNAL LOVE. Kikuchi, Y.; Noriuchi, M. Dept. of Cognitive Neuroscience. Div. of Frontier Health Science. Graduate School of Tokyo Metropolitan University. 7-2-10 Higashi-ogu, Arakawa, Tokyo, Japan. Background: Maternal love, which may be the core of maternal behavior, is essential for the mother-infant attachment relationship and is important for the infantfs development and mental health. However, little has been known about these neural mechanisms in human mothers. We examined patterns of maternal brain activation in response to infant cues using video clips. Methods: We performed functional magnetic resonance imaging (fMRI) measurements while 13 mothers viewed video clips, with no sound, of their own infant and other infants of approximately 16 months of age who demonstrated two different attachment behaviors (smiling at the infantfs mother and crying for her). After the fMRI scan, the mother was asked to rate her feelings (happy, motherly, joyful, warm, love, excited, anxious, etc.) on a five-point scale while watching each video clip. Results: We found that a limited number of the motherfs brain areas were specifically involved in recognition of the motherfs own infant, namely orbitofrontal cortex (OFC), periaqueductal gray, anterior insula, and dorsal and ventrolateral parts of putamen. The magnitude of the activation in response to viewing the motherfs own infant versus other infants in the left OFC was positively correlated with the intensity of joyful (R = .626, p = .022) and happy (R = .635, p = .020), while that in the right OFC was positively correlated with the intensity of anxious (R = .611, p = .027) reported by the mother while viewing video clips of her own infant. Conclusions: Our results showed the highly elaborate neural mechanism mediating maternal love.
Abstract ID: 57
First Name: Noriuchi
Last Name: Madoka
Abstract Title: MATERNAL BRAIN RESPONSES TO INFANTfS CRYING
  
 Abstract:
 MATERNAL BRAIN RESPONSES TO INFANTfS CRYING. Noriuchi, M.; Kikuchi, Y. Dept. of Cognitive Neuroscience. Div. of Frontier Health Science. Graduate School of Tokyo Metropolitan University. 7-2-10 Higashi-ogu, Arakawa, Tokyo, Japan. Background: The neural system mediating maternal behavior of the mother who should protect her infant is a biologically essential mechanism for preservation of the human species. Here, we investigated the neural brain responses of mother by viewing the situation of her own infant in distress, by using fMRI. Methods: We performed functional magnetic resonance imaging (fMRI) measurements while 13 mothers viewed infantsf video clips, with no sound (see the methods of gNEURAL BASIS OF MATERNAL LOVEh in the abstracts). We compared the motherfs brain responses for her own infantfs crying with those for his/her smiling. Results: We found the strong and specific motherfs brain response for the motherfs own infantfs distress. The differential neural activation pattern was found in the dorsal region of OFC, caudate nucleus, right inferior frontal gyrus, dorsomedial prefrontal cortex (PFC), anterior cingulate, posterior cingulate, thalamus, substantia nigra, posterior superior temporal sulcus (STS), and PFC. In addition, the activity level of the left STS or right STS was positively correlated with the intensity of love (R = .624, p = .023) or excited feeling (R = .598, p = .031), respectively. Conclusions: Our findings that a mother responds stronger to cry than smiling of her own infant seem to be biologically meaningful in terms of adaptation to specific demands associated with successful infant care.

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